Skip to content
2000
image of Exosomes in Osteoarthritis: Emerging Roles in Pathogenesis, Diagnosis, and Therapeutic Potential

Abstract

Osteoarthritis (OA) is a leading cause of chronic pain and disability, particularly among the elderly. Despite its high global prevalence, the underlying mechanisms of OA are still not fully understood, and current treatments are largely limited to symptomatic relief. Exosomes, small extracellular vesicles involved in cell-to-cell communication, have recently gained attention for their diagnostic and therapeutic potential in OA. In particular, exosomes derived from Mesenchymal Stem Cells (MSCs) can modulate chondrocyte proliferation, apoptosis, autophagy, and inflammation. Emerging evidence also highlights the role of exosomal non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, in regulating cartilage degradation and subchondral bone remodeling. This review offers a comprehensive synthesis of current knowledge on the role of exosomes in OA, with a unique focus on their dual function as biomarkers and therapeutic tools. We further highlight the promise of exosome-based Drug Delivery Systems (DDSs) and propose future directions for integrating exosome technologies into OA treatment strategies. This work emphasizes the translational potential of exosomes as disease-modifying agents and regenerative tools in osteoarthritis.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128412201251125100451
2026-02-12
2026-02-20
Loading full text...

Full text loading...

References

  1. Shakeri M. Aminian A. Mokhtari K. Unraveling the molecular landscape of osteoarthritis: A comprehensive review focused on the role of non-coding RNAs. Pathol. Res. Pract. 2024 260 155446 10.1016/j.prp.2024.155446 39004001
    [Google Scholar]
  2. Brandt K.D. Radin E.L. Dieppe P.A. van de Putte L. Yet more evidence that osteoarthritis is not a cartilage disease. Ann. Rheum. Dis. 2006 65 10 1261 1264 10.1136/ard.2006.058347 16973787
    [Google Scholar]
  3. Crawford D.C. Miller L.E. Block J.E. Conservative management of symptomatic knee osteoarthritis: A flawed strategy? Orthop. Rev. 2013 5 1 e2 23705060
    [Google Scholar]
  4. Kester B. Minhas S.V. Vigdorchik J.M. Schwarzkopf R. Total knee arthroplasty for posttraumatic osteoarthritis: Is it time for a new classification? J. Arthroplasty 2016 31 8 1649 1653.e1 10.1016/j.arth.2016.02.001 26961087
    [Google Scholar]
  5. Kalluri R. LeBleu V.S. The biology, function, and biomedical applications of exosomes. Science 2020 367 6478 eaau6977 10.1126/science.aau6977 32029601
    [Google Scholar]
  6. Mehrvar A. Akbari M. Khosroshahi E.M. The impact of exosomes on bone health: A focus on osteoporosis. Pathol. Res. Pract. 2024 263 155618 10.1016/j.prp.2024.155618 39362132
    [Google Scholar]
  7. Ni Z. Zhou S. Li S. Exosomes: Roles and therapeutic potential in osteoarthritis. Bone Res. 2020 8 1 25 10.1038/s41413‑020‑0100‑9 32596023
    [Google Scholar]
  8. Raposo G. Nijman H.W. Stoorvogel W. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996 183 3 1161 1172 10.1084/jem.183.3.1161 8642258
    [Google Scholar]
  9. Kibria G. Ramos E.K. Wan Y. Gius D.R. Liu H. Exosomes as a drug delivery system in cancer therapy: Potential and challenges. Mol. Pharm. 2018 15 9 3625 3633 10.1021/acs.molpharmaceut.8b00277 29771531
    [Google Scholar]
  10. Mahaki H. Mansourian M. Meshkat Z. Nanoparticles containing oxaliplatin and the treatment of colorectal cancer. Curr. Pharm. Des. 2023 29 38 3018 3039 10.2174/0113816128274742231103063738 37990895
    [Google Scholar]
  11. Tanzadehpanah H. Mahaki H. Manoochehri H. Soleimani M. Najafi R. AS1411 aptamer improves therapeutic efficacy of PEGylated nanoliposomes loaded with gefitinib in the mice bearing CT26 colon carcinoma. J. Nanopart. Res. 2022 24 12 252 10.1007/s11051‑022‑05630‑0
    [Google Scholar]
  12. Srikanthan S. Li W. Silverstein R.L. McIntyre T.M. Exosome poly‐ubiquitin inhibits platelet activation, downregulates CD36 and inhibits pro‐atherothombotic cellular functions. J. Thromb. Haemost. 2014 12 11 1906 1917 10.1111/jth.12712 25163645
    [Google Scholar]
  13. Hanahan D. Weinberg R.A. Hallmarks of cancer: The next generation. Cell 2011 144 5 646 674 10.1016/j.cell.2011.02.013 21376230
    [Google Scholar]
  14. Rajendran L. Bali J. Barr M.M. Emerging roles of extracellular vesicles in the nervous system. J. Neurosci. 2014 34 46 15482 15489 10.1523/JNEUROSCI.3258‑14.2014 25392515
    [Google Scholar]
  15. Toh W.S. Foldager C.B. Pei M. Hui J.H.P. Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration. Stem Cell Rev. 2014 10 5 686 696 10.1007/s12015‑014‑9526‑z 24869958
    [Google Scholar]
  16. Zhu Y. Wang Y. Zhao B. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res. Ther. 2017 8 1 64 10.1186/s13287‑017‑0510‑9 28279188
    [Google Scholar]
  17. Cosenza S. Ruiz M. Toupet K. Jorgensen C. Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci. Rep. 2017 7 1 16214 10.1038/s41598‑017‑15376‑8 29176667
    [Google Scholar]
  18. Reddy V.S. Madala S.K. Trinath J. Reddy G.B. Extracellular small heat shock proteins: Exosomal biogenesis and function. Cell Stress Chaperones 2018 23 3 441 454 10.1007/s12192‑017‑0856‑z 29086335
    [Google Scholar]
  19. Tobón-Arroyave S.I. Celis-Mejía N. Córdoba-Hidalgo M.P. Isaza-Guzmán D.M. Decreased salivary concentration of CD 9 and CD 81 exosome‐related tetraspanins may be associated with the periodontal clinical status. J. Clin. Periodontol. 2019 46 4 470 480 10.1111/jcpe.13099 30825338
    [Google Scholar]
  20. Fan S.J. Kroeger B. Marie P.P. Glutamine deprivation alters the origin and function of cancer cell exosomes. EMBO J. 2020 39 16 e103009 10.15252/embj.2019103009 32720716
    [Google Scholar]
  21. Théry C. Zitvogel L. Amigorena S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002 2 8 569 579 10.1038/nri855 12154376
    [Google Scholar]
  22. Meldolesi J. Exosomes and ectosomes in intercellular communication. Curr. Biol. 2018 28 8 R435 R444 10.1016/j.cub.2018.01.059 29689228
    [Google Scholar]
  23. van Niel G. D’Angelo G. Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 2018 19 4 213 228 10.1038/nrm.2017.125 29339798
    [Google Scholar]
  24. Schöneberg J. Lee I.H. Iwasa J.H. Hurley J.H. Reverse-topology membrane scission by the ESCRT proteins. Nat. Rev. Mol. Cell Biol. 2017 18 1 5 17 10.1038/nrm.2016.121 27703243
    [Google Scholar]
  25. Vietri M. Radulovic M. Stenmark H. The many functions of ESCRTs. Nat. Rev. Mol. Cell Biol. 2020 21 1 25 42 10.1038/s41580‑019‑0177‑4 31705132
    [Google Scholar]
  26. Wei D. Zhan W. Gao Y. RAB31 marks and controls an ESCRT-independent exosome pathway. Cell Res. 2021 31 2 157 177 10.1038/s41422‑020‑00409‑1 32958903
    [Google Scholar]
  27. Ostrowski M Carmo NB Krumeich S Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2010 12 1 19-30 1-13 10.1038/ncb2000 19966785
    [Google Scholar]
  28. Song L. Tang S. Han X. KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a. Nat. Commun. 2019 10 1 1639 10.1038/s41467‑019‑09720‑x 30967557
    [Google Scholar]
  29. O’Brien K. Breyne K. Ughetto S. Laurent L.C. Breakefield X.O. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat. Rev. Mol. Cell Biol. 2020 21 10 585 606 10.1038/s41580‑020‑0251‑y 32457507
    [Google Scholar]
  30. Raimondo F. Morosi L. Chinello C. Magni F. Pitto M. Advances in membranous vesicle and exosome proteomics improving biological understanding and biomarker discovery. Proteomics 2011 11 4 709 720 10.1002/pmic.201000422 21241021
    [Google Scholar]
  31. Zhou Y. Ming J. Li Y. Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis. Cell Death Discov. 2021 7 1 37 10.1038/s41420‑021‑00418‑y 33627637
    [Google Scholar]
  32. Liu B. Xian Y. Chen X. Inflammatory fibroblast‐like synoviocyte‐derived exosomes aggravate osteoarthritis via enhancing macrophage glycolysis. Adv. Sci. 2024 11 14 2307338 10.1002/advs.202307338 38342630
    [Google Scholar]
  33. Li P. Kaslan M. Lee S.H. Yao J. Gao Z. Progress in exosome isolation techniques. Theranostics 2017 7 3 789 804 10.7150/thno.18133 28255367
    [Google Scholar]
  34. Konoshenko M.Y. Lekchnov E.A. Vlassov A.V. Laktionov P.P. Isolation of extracellular vesicles: General methodologies and latest trends. BioMed Res. Int. 2018 2018 1 1 27 10.1155/2018/8545347 29662902
    [Google Scholar]
  35. Zhang P. He M. Zeng Y. Ultrasensitive microfluidic analysis of circulating exosomes using a nanostructured graphene oxide/] polydopamine coating. Lab Chip 2016 16 16 3033 3042 10.1039/C6LC00279J 27045543
    [Google Scholar]
  36. Guay C. Regazzi R. Exosomes as new players in metabolic organ cross‐talk. Diabetes Obes. Metab. 2017 19 S1 137 146 10.1111/dom.13027 28880477
    [Google Scholar]
  37. Hoshino A. Costa-Silva B. Shen T.L. Tumour exosome integrins determine organotropic metastasis. Nature 2015 527 7578 329 335 10.1038/nature15756 26524530
    [Google Scholar]
  38. Sheykhhasan M. Ahmadieh-Yazdi A. Heidari R. Revolutionizing cancer treatment: The power of dendritic cell-based vaccines in immunotherapy. Biomed. Pharmacother. 2025 184 117858 10.1016/j.biopha.2025.117858 39955851
    [Google Scholar]
  39. Chen G. Huang A.C. Zhang W. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018 560 7718 382 386 10.1038/s41586‑018‑0392‑8 30089911
    [Google Scholar]
  40. Lugini L. Cecchetti S. Huber V. Immune surveillance properties of human NK cell-derived exosomes. J. Immunol. 2012 189 6 2833 2842 10.4049/jimmunol.1101988 22904309
    [Google Scholar]
  41. Kim S.H. Bianco N.R. Shufesky W.J. Morelli A.E. Robbins P.D. MHC class II+ exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J. Immunol. 2007 179 4 2235 2241 10.4049/jimmunol.179.4.2235 17675484
    [Google Scholar]
  42. Rivoltini L. Chiodoni C. Squarcina P. TNF-related apoptosis-inducing ligand (TRAIL)-armed exosomes deliver proapoptotic signals to tumor site. Clin. Cancer Res. 2016 22 14 3499 3512 10.1158/1078‑0432.CCR‑15‑2170 26944067
    [Google Scholar]
  43. McGough I.J. Vincent J.P. Exosomes in developmental signalling. Development 2016 143 14 2482 2493 10.1242/dev.126516 27436038
    [Google Scholar]
  44. Sheldon H. Heikamp E. Turley H. New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 2010 116 13 2385 2394 10.1182/blood‑2009‑08‑239228 20558614
    [Google Scholar]
  45. Raimondo S. Saieva L. Corrado C. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun. Signal. 2015 13 1 8 10.1186/s12964‑015‑0086‑x 25644060
    [Google Scholar]
  46. Yu L. Yang F. Jiang L. Exosomes with membrane‐associated TGF‐β1 from gene‐modified dendritic cells inhibit murine EAE independently of MHC restriction. Eur. J. Immunol. 2013 43 9 2461 2472 10.1002/eji.201243295 23716181
    [Google Scholar]
  47. Jamialahmadi H Nazari SE TanzadehPanah H Targeting transforming growth factor beta (TGF-β) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer. Sci. Rep. 2023 13 1 14357 10.1038/s41598‑023‑41550‑2 37658230
    [Google Scholar]
  48. Taverna S. Pucci M. Giallombardo M. Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway. Sci. Rep. 2017 7 1 3170 10.1038/s41598‑017‑03460‑y 28600504
    [Google Scholar]
  49. Corrado C. Saieva L. Raimondo S. Santoro A. De Leo G. Alessandro R. Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor. J. Cell. Mol. Med. 2016 20 10 1829 1839 10.1111/jcmm.12873 27196940
    [Google Scholar]
  50. Montecalvo A. Larregina A.T. Shufesky W.J. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 2012 119 3 756 766 10.1182/blood‑2011‑02‑338004 22031862
    [Google Scholar]
  51. Mulcahy L.A. Pink R.C. Carter D.R.F. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 2014 3 1 24641 10.3402/jev.v3.24641 25143819
    [Google Scholar]
  52. McKelvey K.J. Powell K.L. Ashton A.W. Morris J.M. McCracken S.A. Exosomes: Mechanisms of uptake. J. Circ. Biomark. 2015 4 7 10.5772/61186 28936243
    [Google Scholar]
  53. Kaksonen M. Roux A. Mechanisms of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 2018 19 5 313 326 10.1038/nrm.2017.132 29410531
    [Google Scholar]
  54. Tian T. Zhu Y.L. Zhou Y.Y. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery. J. Biol. Chem. 2014 289 32 22258 22267 10.1074/jbc.M114.588046 24951588
    [Google Scholar]
  55. Svensson K.J. Christianson H.C. Wittrup A. Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1. J. Biol. Chem. 2013 288 24 17713 17724 10.1074/jbc.M112.445403 23653359
    [Google Scholar]
  56. Santos M.F. Rappa G. Karbanová J. Kurth T. Corbeil D. Lorico A. VAMP-associated protein-A and oxysterol-binding protein–related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum. J. Biol. Chem. 2018 293 36 13834 13848 10.1074/jbc.RA118.003725 30018135
    [Google Scholar]
  57. Rappa G. Santos M.F. Green T.M. Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes. Oncotarget 2017 8 9 14443 14461 10.18632/oncotarget.14804 28129640
    [Google Scholar]
  58. Andreu Z. Yáñez-Mó M. Tetraspanins in extracellular vesicle formation and function. Front. Immunol. 2014 5 442 10.3389/fimmu.2014.00442 25278937
    [Google Scholar]
  59. Tanzadehpanah H. Bahmani A. Hosseinpour Moghadam N. Synthesis, anticancer activity, and β‐lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches. Luminescence 2021 36 1 117 128 10.1002/bio.3929 32725773
    [Google Scholar]
  60. Song X. Ding Y. Liu G. Cancer cell-derived exosomes induce mitogen-activated protein kinase-dependent monocyte survival by transport of functional receptor tyrosine kinases. J. Biol. Chem. 2016 291 16 8453 8464 10.1074/jbc.M116.716316 26895960
    [Google Scholar]
  61. Melo S.A. Sugimoto H. O’Connell J.T. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 2014 26 5 707 721 10.1016/j.ccell.2014.09.005 25446899
    [Google Scholar]
  62. Greening D.W. Nguyen H.P.T. Elgass K. Simpson R.J. Salamonsen L.A. Human endometrial exosomes contain hormone-specific cargo modulating trophoblast adhesive capacity: Insights into endometrial-embryo interactions. Biol. Reprod. 2016 94 2 38 10.1095/biolreprod.115.134890 26764347
    [Google Scholar]
  63. Crewe C. Joffin N. Rutkowski J.M. An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state. Cell 2018 175 3 695 708.e13 10.1016/j.cell.2018.09.005 30293865
    [Google Scholar]
  64. Choi D.S. Kim D.K. Kim Y.K. Gho Y.S. Proteomics of extracellular vesicles: Exosomes and ectosomes. Mass Spectrom. Rev. 2015 34 4 474 490 10.1002/mas.21420 24421117
    [Google Scholar]
  65. Conigliaro A. Fontana S. Raimondo S. Alessandro R. Exosomes: Nanocarriers of biological messages. Adv. Exp. Med. Biol. 2017 998 23 43 10.1007/978‑981‑10‑4397‑0_2
    [Google Scholar]
  66. Pegtel D.M. Cosmopoulos K. Thorley-Lawson D.A. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA 2010 107 14 6328 6333 10.1073/pnas.0914843107 20304794
    [Google Scholar]
  67. Chow A. Zhou W. Liu L. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-κB. Sci. Rep. 2014 4 1 5750 10.1038/srep05750 25034888
    [Google Scholar]
  68. Chen T.S. Lai R.C. Lee M.M. Choo A.B.H. Lee C.N. Lim S.K. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res. 2010 38 1 215 224 10.1093/nar/gkp857 19850715
    [Google Scholar]
  69. Ma T. Chen Y. Chen Y. MicroRNA‐132, delivered by mesenchymal stem cell‐derived exosomes, promote angiogenesis in myocardial infarction. Stem Cells Int. 2018 2018 1 1 11 10.1155/2018/3290372 30271437
    [Google Scholar]
  70. Caruso S. Poon I.K.H. Apoptotic cell-derived extracellular vesicles: More than just debris. Front. Immunol. 2018 9 1486 10.3389/fimmu.2018.01486 30002658
    [Google Scholar]
  71. Tkach M. Théry C. Communication by extracellular vesicles: Where we are and where we need to go. Cell 2016 164 6 1226 1232 10.1016/j.cell.2016.01.043 26967288
    [Google Scholar]
  72. de Lange-Brokaar B.J.E. Ioan-Facsinay A. van Osch G.J.V.M. Synovial inflammation, immune cells and their cytokines in osteoarthritis: A review. Osteoarthritis Cartilage 2012 20 12 1484 1499 10.1016/j.joca.2012.08.027 22960092
    [Google Scholar]
  73. Haywood L. McWilliams D.F. Pearson C.I. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 2003 48 8 2173 2177 10.1002/art.11094 12905470
    [Google Scholar]
  74. Griffin TM Scanzello CR Innate inflammation and synovial macrophages in osteoarthritis pathophysiology. Clin Exp Rheumatol 2019 37 5 57 63 (Suppl. 120) 31621560
    [Google Scholar]
  75. Domenis R. Zanutel R. Caponnetto F. Characterization of the proinflammatory profile of synovial fluid‐derived exosomes of patients with osteoarthritis. Mediators Inflamm. 2017 2017 1 1 11 10.1155/2017/4814987 28634420
    [Google Scholar]
  76. Kato T. Miyaki S. Ishitobi H. Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes. Arthritis Res. Ther. 2014 16 4 R163 10.1186/ar4679 25092378
    [Google Scholar]
  77. Xie F. Liu Y. Chen X. Role of MicroRNA, LncRNA, and exosomes in the progression of osteoarthritis: A review of recent literature. Orthop. Surg. 2020 12 3 708 716 10.1111/os.12690 32436304
    [Google Scholar]
  78. Wang R. Shiu H.T. Lee W.Y.W. Emerging role of lncRNAs in osteoarthritis: An updated review. Front. Immunol. 2022 13 982773 10.3389/fimmu.2022.982773 36304464
    [Google Scholar]
  79. Sheykhhasan M. Ahmadyousefi Y. Seyedebrahimi R. DLX6-AS1: A putative lncRNA candidate in multiple human cancers. Expert Rev. Mol. Med. 2021 23 e17 10.1017/erm.2021.17 34823630
    [Google Scholar]
  80. Sheykhhasan M. Tanzadehpanah H. Ahmadieh Yazdi A. FLVCR1-AS1 and FBXL19-AS1: Two putative lncRNA candidates in multiple human cancers. Noncoding RNA 2022 9 1 1 10.3390/ncrna9010001 36649030
    [Google Scholar]
  81. Wu J. Kuang L. Chen C. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials 2019 206 87 100 10.1016/j.biomaterials.2019.03.022 30927715
    [Google Scholar]
  82. Mao G. Zhang Z. Hu S. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res. Ther. 2018 9 1 247 10.1186/s13287‑018‑1004‑0 30257711
    [Google Scholar]
  83. Yan L. Liu G. Wu X. The umbilical cord mesenchymal stem cell‐derived exosomal lncRNA H19 improves osteochondral activity through miR‐29b‐3p/FoxO3 axis. Clin. Transl. Med. 2021 11 1 e255 10.1002/ctm2.255 33463060
    [Google Scholar]
  84. Liu Q. Wang R. Hou S. Chondrocyte-derived exosomes promote cartilage calcification in temporomandibular joint osteoarthritis. Arthritis Res. Ther. 2022 24 1 44 10.1186/s13075‑022‑02738‑5 35164837
    [Google Scholar]
  85. Liu H. Chen Y. Huang Y. Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through mTOR signaling. J. Nanobiotechnology 2024 22 1 197 10.1186/s12951‑024‑02444‑1 38644475
    [Google Scholar]
  86. Yu F.Y. Xie C.Q. Jiang C. MiR-92a inhibits fibroblast-like synoviocyte proliferation and migration in rheumatoid arthritis by targeting AKT2. J. Biosci. 2018 43 5 911 919 10.1007/s12038‑018‑9803‑0 30541951
    [Google Scholar]
  87. Zou Y. Xu H. Involvement of long noncoding RNAs in the pathogenesis of autoimmune diseases. J. Transl. Autoimmun. 2020 3 100044 10.1016/j.jtauto.2020.100044 32743525
    [Google Scholar]
  88. Yang R.Z. Zheng H.L. Xu W.N. Vascular endothelial cell-secreted exosomes facilitate osteoarthritis pathogenesis by promoting chondrocyte apoptosis. Aging 2021 13 3 4647 4662 10.18632/aging.202506 33526719
    [Google Scholar]
  89. Kolhe R. Hunter M. Liu S. Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci. Rep. 2017 7 1 2029 10.1038/s41598‑017‑01905‑y 28515465
    [Google Scholar]
  90. Zhou L. Ye H. Liu L. Chen Y. Human Bone mesenchymal stem cell-derived exosomes inhibit IL-1β-induced inflammation in osteoarthritis chondrocytes. Cell J. 2021 23 4 485 494 34455725
    [Google Scholar]
  91. Mathieu M. Martin-Jaular L. Lavieu G. Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat. Cell Biol. 2019 21 1 9 17 10.1038/s41556‑018‑0250‑9 30602770
    [Google Scholar]
  92. Tai Y.L. Chen K.C. Hsieh J.T. Shen T.L. Exosomes in cancer development and clinical applications. Cancer Sci. 2018 109 8 2364 2374 10.1111/cas.13697 29908100
    [Google Scholar]
  93. Deng H. Sun C. Sun Y. Lipid, protein, and microRNA composition within mesenchymal stem cell-derived exosomes. Cell. Reprogram. 2018 20 3 178 186 10.1089/cell.2017.0047 29782191
    [Google Scholar]
  94. Zhang Z.G. Buller B. Chopp M. Exosomes — Beyond stem cells for restorative therapy in stroke and neurological injury. Nat. Rev. Neurol. 2019 15 4 193 203 10.1038/s41582‑018‑0126‑4 30700824
    [Google Scholar]
  95. Lin Z. Rodriguez N.E. Zhao J. Selective enrichment of microRNAs in extracellular matrix vesicles produced by growth plate chondrocytes. Bone 2016 88 47 55 10.1016/j.bone.2016.03.018 27080510
    [Google Scholar]
  96. Mitton E. Gohr C.M. McNally M.T. Rosenthal A.K. Articular cartilage vesicles contain RNA. Biochem. Biophys. Res. Commun. 2009 388 3 533 538 10.1016/j.bbrc.2009.08.038 19679100
    [Google Scholar]
  97. Wang R. Xu B. Xu H. TGF-β1 promoted chondrocyte proliferation by regulating Sp1 through MSC-exosomes derived miR-135b. Cell Cycle 2018 17 24 2756 2765 10.1080/15384101.2018.1556063 30526325
    [Google Scholar]
  98. Tao S.C. Yuan T. Zhang Y.L. Yin W.J. Guo S.C. Zhang C.Q. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 2017 7 1 180 195 10.7150/thno.17133 28042326
    [Google Scholar]
  99. Ni Z. Kuang L. Chen H. The exosome-like vesicles from osteoarthritic chondrocyte enhanced mature IL-1β production of macrophages and aggravated synovitis in osteoarthritis. Cell Death Dis. 2019 10 7 522 10.1038/s41419‑019‑1739‑2 31285423
    [Google Scholar]
  100. Wang M. Zhou L. Yu F. Zhang Y. Li P. Wang K. The functional roles of exosomal long non-coding RNAs in cancer. Cell. Mol. Life Sci. 2019 76 11 2059 2076 10.1007/s00018‑019‑03018‑3 30683984
    [Google Scholar]
  101. Zhao Y. Xu J. Synovial fluid-derived exosomal lncRNA PCGEM1 as biomarker for the different stages of osteoarthritis. Int. Orthop. 2018 42 12 2865 2872 10.1007/s00264‑018‑4093‑6 30128669
    [Google Scholar]
  102. Liu Y. Zou R. Wang Z. Wen C. Zhang F. Lin F. Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis. Biochem. J. 2018 475 22 3629 3638 10.1042/BCJ20180675 30341166
    [Google Scholar]
  103. Liu Y. Lin L. Zou R. Wen C. Wang Z. Lin F. MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis. Cell Cycle 2018 17 21-22 2411 2422 10.1080/15384101.2018.1526603 30324848
    [Google Scholar]
  104. Meng Y. Qiu S. Sun L. Zuo J. Knockdown of exosome mediated lnc PVT1 alleviates lipopolysaccharide induced osteoarthritis progression by mediating the HMGB1/TLR4/NF κB pathway via miR 93 5p. Mol. Med. Rep. 2020 22 6 5313 5325 10.3892/mmr.2020.11594 33174011
    [Google Scholar]
  105. Yang Q. Yao Y. Zhao D. LncRNA H19 secreted by umbilical cord blood mesenchymal stem cells through microRNA-29a-3p/FOS axis for central sensitization of pain in advanced osteoarthritis. Am. J. Transl. Res. 2021 13 3 1245 1256 33841653
    [Google Scholar]
  106. Guo Z. Wang H. Zhao F. Exosomal circ-BRWD1 contributes to osteoarthritis development through the modulation of miR-1277/TRAF6 axis. Arthritis Res. Ther. 2021 23 1 159 10.1186/s13075‑021‑02541‑8 34082824
    [Google Scholar]
  107. Li S. Liu J. Liu S. Jiao W. Wang X. Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis. J. Nanobiotechnology 2021 19 1 194 10.1186/s12951‑021‑00940‑2 34193158
    [Google Scholar]
  108. Zhu C. Shen K. Zhou W. Wu H. Lu Y. Exosome-mediated circ_0001846 participates in IL-1β-induced chondrocyte cell damage by miR-149-5p-dependent regulation of WNT5B. Clin. Immunol. 2021 232 108856 10.1016/j.clim.2021.108856 34536574
    [Google Scholar]
  109. Mao G. Xu Y. Long D. Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis. Stem Cell Res. Ther. 2021 12 1 389 10.1186/s13287‑021‑02431‑5 34256841
    [Google Scholar]
  110. Tao S.C. Huang J.Y. Gao Y. Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis. Bioact. Mater. 2021 6 12 4455 4469 10.1016/j.bioactmat.2021.04.031 34027234
    [Google Scholar]
  111. Mouw J.K. Ou G. Weaver V.M. Extracellular matrix assembly: A multiscale deconstruction. Nat. Rev. Mol. Cell Biol. 2014 15 12 771 785 10.1038/nrm3902 25370693
    [Google Scholar]
  112. Liu-Bryan R. Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat. Rev. Rheumatol. 2015 11 1 35 44 10.1038/nrrheum.2014.162 25266449
    [Google Scholar]
  113. Latourte A. Cherifi C. Maillet J. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann. Rheum. Dis. 2017 76 4 748 755 10.1136/annrheumdis‑2016‑209757 27789465
    [Google Scholar]
  114. Glasson S.S. Askew R. Sheppard B. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005 434 7033 644 648 10.1038/nature03369 15800624
    [Google Scholar]
  115. Little C.B. Barai A. Burkhardt D. Matrix metalloproteinase 13–deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum. 2009 60 12 3723 3733 10.1002/art.25002 19950295
    [Google Scholar]
  116. Goldring M.B. Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract. Res. Clin. Rheumatol. 2006 20 5 1003 1025 10.1016/j.berh.2006.06.003 16980220
    [Google Scholar]
  117. Hwang H. Kim H. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int. J. Mol. Sci. 2015 16 11 26035 26054 10.3390/ijms161125943 26528972
    [Google Scholar]
  118. Li X. Wang Y. Cai Z. Zhou Q. Li L. Fu P. Exosomes from human umbilical cord mesenchymal stem cells inhibit ROS production and cell apoptosis in human articular chondrocytes via the miR‐100‐5p/NOX4 axis. Cell Biol. Int. 2021 45 10 2096 2106 10.1002/cbin.11657 34197004
    [Google Scholar]
  119. Wang X. Li Z. Cui Y. Cui X. Chen C. Wang Z. Exosomes isolated from bone marrow mesenchymal stem cells exert a protective effect on osteoarthritis via lncRNA LYRM4-AS1-GRPR-miR-6515-5p. Front. Cell Dev. Biol. 2021 9 644380 10.3389/fcell.2021.644380 34124036
    [Google Scholar]
  120. Xie J. Huang Z. Yu X. Zhou L. Pei F. Clinical implications of macrophage dysfunction in the development of osteoarthritis of the knee. Cytokine Growth Factor Rev. 2019 46 36 44 10.1016/j.cytogfr.2019.03.004 30910350
    [Google Scholar]
  121. Asghar S. Litherland G. Meek D. Lockhart J. Goodyear C. Crilly A. The synovial secretome contributes to cartilage pathology in osteoarthritis: A role for exosomes. Osteoarthritis Cartilage 2018 26 S131 S132 10.1016/j.joca.2018.02.286
    [Google Scholar]
  122. Gross J.C. Chaudhary V. Bartscherer K. Boutros M. Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 2012 14 10 1036 1045 10.1038/ncb2574 22983114
    [Google Scholar]
  123. Buschow S.I. Liefhebber J.M.P. Wubbolts R. Stoorvogel W. Exosomes contain ubiquitinated proteins. Blood Cells Mol. Dis. 2005 35 3 398 403 10.1016/j.bcmd.2005.08.005 16203162
    [Google Scholar]
  124. Zhang S. Chuah S.J. Lai R.C. Hui J.H.P. Lim S.K. Toh W.S. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials 2018 156 16 27 10.1016/j.biomaterials.2017.11.028 29182933
    [Google Scholar]
  125. Withrow J. Murphy C. Liu Y. Hunter M. Fulzele S. Hamrick M.W. Extracellular vesicles in the pathogenesis of rheumatoid arthritis and osteoarthritis. Arthritis Res. Ther. 2016 18 1 286 10.1186/s13075‑016‑1178‑8 27906035
    [Google Scholar]
  126. Rashidi N. Liu C. Guillot P.V. Tamaddon M. Isolation, characterization, and in vitro cell studies of plant-based exosome-like nanovesicles for treatment of early osteoarthritis. Int. J. Mol. Sci. 2025 26 5 2211 10.3390/ijms26052211 40076829
    [Google Scholar]
  127. Veziroglu E.M. Mias G.I. Characterizing extracellular vesicles and their diverse RNA contents. Front. Genet. 2020 11 700 10.3389/fgene.2020.00700 32765582
    [Google Scholar]
  128. Akers J.C. Gonda D. Kim R. Carter B.S. Chen C.C. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol. 2013 113 1 1 11 10.1007/s11060‑013‑1084‑8 23456661
    [Google Scholar]
  129. Gao K. Zhu W. Li H. Association between cytokines and exosomes in synovial fluid of individuals with knee osteoarthritis. Mod. Rheumatol. 2020 30 4 758 764 10.1080/14397595.2019.1651445 31370732
    [Google Scholar]
  130. Headland S.E. Jones H.R. Norling L.V. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci. Transl. Med. 2015 7 315 315ra190 10.1126/scitranslmed.aac5608 26606969
    [Google Scholar]
  131. Anderson H.C. Matrix vesicles and calcification. Curr. Rheumatol. Rep. 2003 5 3 222 226 10.1007/s11926‑003‑0071‑z 12744815
    [Google Scholar]
  132. Jubeck B. Gohr C. Fahey M. Promotion of articular cartilage matrix vesicle mineralization by type I collagen. Arthritis Rheum. 2008 58 9 2809 2817 10.1002/art.23762 18759309
    [Google Scholar]
  133. Shapiro I.M. Landis W.J. Risbud M.V. Matrix vesicles: Are they anchored exosomes? Bone 2015 79 29 36 10.1016/j.bone.2015.05.013 25980744
    [Google Scholar]
  134. Zheng L. Wang Y. Qiu P. Primary chondrocyte exosomes mediate osteoarthritis progression by regulating mitochondrion and immune reactivity. Nanomedicine 2019 14 24 3193 3212 10.2217/nnm‑2018‑0498 31855117
    [Google Scholar]
  135. Song J. Kang Y. Chun C-H. Jin E-J. Selective loading of exosomal HULC and miR-372 is responsible for chondrocyte death during OA pathogenesis. Anim. Cells Syst. 2017 21 6 397 403 10.1080/19768354.2017.1406871
    [Google Scholar]
  136. Baker K. Grainger A. Niu J. Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann. Rheum. Dis. 2010 69 10 1779 1783 10.1136/ard.2009.121426 20472593
    [Google Scholar]
  137. Benito M.J. Veale D.J. FitzGerald O. van den Berg W.B. Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann. Rheum. Dis. 2005 64 9 1263 1267 10.1136/ard.2004.025270 15731292
    [Google Scholar]
  138. Tsuno H. Suematsu N. Sato T. Effects of methotrexate and salazosulfapyridine on protein profiles of exosomes derived from a human synovial sarcoma cell line of SW982. Proteomics Clin. Appl. 2016 10 2 164 171 10.1002/prca.201500064 26172530
    [Google Scholar]
  139. Castañeda S. Roman-Blas J.A. Largo R. Herrero-Beaumont G. Subchondral bone as a key target for osteoarthritis treatment. Biochem. Pharmacol. 2012 83 3 315 323 10.1016/j.bcp.2011.09.018 21964345
    [Google Scholar]
  140. Stewart H.L. Kawcak C.E. The importance of subchondral bone in the pathophysiology of osteoarthritis. Front. Vet. Sci. 2018 5 178 10.3389/fvets.2018.00178 30211173
    [Google Scholar]
  141. Maas O. Joseph G.B. Sommer G. Wild D. Kretzschmar M. Association between cartilage degeneration and subchondral bone remodeling in patients with knee osteoarthritis comparing MRI and 99m Tc-DPD-SPECT/CT. Osteoarthritis Cartilage 2015 23 10 1713 1720 10.1016/j.joca.2015.05.014 26028141
    [Google Scholar]
  142. Barr A.J. Campbell T.M. Hopkinson D. Kingsbury S.R. Bowes M.A. Conaghan P.G. A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res. Ther. 2015 17 1 228 10.1186/s13075‑015‑0735‑x 26303219
    [Google Scholar]
  143. Cui Z. Crane J. Xie H. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone. Ann. Rheum. Dis. 2016 75 9 1714 1721 10.1136/annrheumdis‑2015‑207923 26470720
    [Google Scholar]
  144. Xu T. Xu M. Bai J. Tenocyte-derived exosomes induce the tenogenic differentiation of mesenchymal stem cells through TGF-β. Cytotechnology 2019 71 1 57 65 10.1007/s10616‑018‑0264‑y 30599073
    [Google Scholar]
  145. Cai Z. Zhang W. Yang F. Immunosuppressive exosomes from TGF-β1 gene-modified dendritic cells attenuate Th17-mediated inflammatory autoimmune disease by inducing regulatory T cells. Cell Res. 2012 22 3 607 610 10.1038/cr.2011.196 22157651
    [Google Scholar]
  146. Gandhi R. Takahashi M. Virtanen C. Syed K. Davey J.R. Mahomed N.N. Microarray analysis of the infrapatellar fat pad in knee osteoarthritis: Relationship with joint inflammation. J. Rheumatol. 2011 38 9 1966 1972 10.3899/jrheum.101302 21765106
    [Google Scholar]
  147. Cai J. Xu J. Wang K. Association between infrapatellar fat pad volume and knee structural changes in patients with knee osteoarthritis. J. Rheumatol. 2015 42 10 1878 1884 10.3899/jrheum.150175 26276969
    [Google Scholar]
  148. Ballegaard C. Riis R.G.C. Bliddal H. Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: A cross-sectional study. Osteoarthritis Cartilage 2014 22 7 933 940 10.1016/j.joca.2014.04.018 24821663
    [Google Scholar]
  149. Koh Y.G. Choi Y.J. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee 2012 19 6 902 907 10.1016/j.knee.2012.04.001 22583627
    [Google Scholar]
  150. Ibrahim M. Kartus J.T. Steigen S.E. Olsen R. Meknas K. More tendon degeneration in patients with shoulder osteoarthritis. Knee Surg. Sports Traumatol. Arthrosc. 2019 27 1 267 275 10.1007/s00167‑018‑5186‑x 30284007
    [Google Scholar]
  151. Meknas K. Johansen O. Steigen S.E. Olsen R. Jørgensen L. Kartus J. Could tendinosis be involved in osteoarthritis? Scand. J. Med. Sci. Sports 2012 22 5 627 634 10.1111/j.1600‑0838.2010.01287.x 21410541
    [Google Scholar]
  152. Wang Y. He G. Guo Y. Exosomes from tendon stem cells promote injury tendon healing through balancing synthesis and degradation of the tendon extracellular matrix. J. Cell. Mol. Med. 2019 23 8 5475 5485 10.1111/jcmm.14430 31148334
    [Google Scholar]
  153. Schulze-Tanzil G. Intraarticular ligament degeneration is interrelated with cartilage and bone destruction in osteoarthritis. Cells 2019 8 9 990 10.3390/cells8090990 31462003
    [Google Scholar]
  154. Hill C.L. Seo G.S. Gale D. Totterman S. Gale M.E. Felson D.T. Cruciate ligament integrity in osteoarthritis of the knee. Arthritis Rheum. 2005 52 3 794 799 10.1002/art.20943 15751064
    [Google Scholar]
  155. Zhao L.R. Mao J.Q. Zhao B.J. Chen J. Isolation and biological characteristics of exosomes derived from periodontal ligament stem cells. Shanghai J Stomatol 2019 28 4 343 348 31792471
    [Google Scholar]
  156. Zhao M. Dai W. Wang H. Periodontal ligament fibroblasts regulate osteoblasts by exosome secretion induced by inflammatory stimuli. Arch. Oral Biol. 2019 105 27 34 10.1016/j.archoralbio.2019.06.002 31247478
    [Google Scholar]
  157. Lee W.Y. Wang B. Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives. J. Orthop. Translat. 2017 9 76 88 10.1016/j.jot.2017.03.005 29662802
    [Google Scholar]
  158. Di Matteo B. Vandenbulcke F. Vitale N.D. Minimally manipulated mesenchymal stem cells for the treatment of knee osteoarthritis: A systematic review of clinical evidence. Stem Cells Int. 2019 2019 1 1 14 10.1155/2019/1735242 31485234
    [Google Scholar]
  159. He L. He T. Xing J. Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis. Stem Cell Res. Ther. 2020 11 1 276 10.1186/s13287‑020‑01781‑w 32650828
    [Google Scholar]
  160. Long L. Zou G. Cheng Y. Li F. Wu H. Shen Y. MATN3 delivered by exosome from synovial mesenchymal stem cells relieves knee osteoarthritis: Evidence from in vitro and in vivo studies. J. Orthop. Translat. 2023 41 20 32 10.1016/j.jot.2023.06.003 37635810
    [Google Scholar]
  161. Su W-T. Ko C-S. Chen J-H. Stem cells from human exfoliated deciduous teeth: A concise review. Curr. Stem Cell Res. Ther. 2020 15 1 61 76 10.2174/1574888X14666191018122109 31648649
    [Google Scholar]
  162. Xu Y. Shen L. Li F. Yang J. Wan X. Ouyang M. microRNA‐16‐5p‐containing exosomes derived from bone marrow‐derived mesenchymal stem cells inhibit proliferation, migration, and invasion, while promoting apoptosis of colorectal cancer cells by downregulating ITGA2. J. Cell. Physiol. 2019 234 11 21380 21394 10.1002/jcp.28747 31102273
    [Google Scholar]
  163. Xie C. Du L.Y. Guo F. Li X. Cheng B. Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells suppress oral cancer cell proliferation, invasion, and migration. Mol. Cell. Biochem. 2019 458 1-2 11 26 10.1007/s11010‑019‑03526‑7 31165315
    [Google Scholar]
  164. He J.G. Xie Q.L. Li B.B. Zhou L. Yan D. Exosomes derived from IDO1-overexpressing rat bone marrow mesenchymal stem cells promote immunotolerance of cardiac allografts. Cell Transplant. 2018 27 11 1657 1683 10.1177/0963689718805375 30311501
    [Google Scholar]
  165. Zhao C. Zhou X. Qiu J. Exosomes derived from bone marrow mesenchymal stem cells inhibit complement activation in rats with spinal cord injury. Drug Des. Devel. Ther. 2019 13 3693 3704 10.2147/DDDT.S209636 31695336
    [Google Scholar]
  166. Rong X. Liu J. Yao X. Jiang T. Wang Y. Xie F. Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway. Stem Cell Res. Ther. 2019 10 1 98 10.1186/s13287‑019‑1204‑2 30885249
    [Google Scholar]
  167. Qi H. Liu D.P. Xiao D.W. Tian D.C. Su Y.W. Jin S.F. Exosomes derived from mesenchymal stem cells inhibit mitochondrial dysfunction-induced apoptosis of chondrocytes via p38, ERK, and Akt pathways. In Vitro Cell. Dev. Biol. Anim. 2019 55 3 203 210 10.1007/s11626‑019‑00330‑x 30783864
    [Google Scholar]
  168. Chen P. Zheng L. Wang Y. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics 2019 9 9 2439 2459 10.7150/thno.31017 31131046
    [Google Scholar]
  169. Kurth T. Hedbom E. Shintani N. Chondrogenic potential of human synovial mesenchymal stem cells in alginate. Osteoarthritis Cartilage 2007 15 10 1178 1189 10.1016/j.joca.2007.03.015 17502159
    [Google Scholar]
  170. Shirasawa S. Sekiya I. Sakaguchi Y. Yagishita K. Ichinose S. Muneta T. In vitro chondrogenesis of human synovium-derived mesenchymal stem cells: Optimal condition and comparison with bone marrow-derived cells. J. Cell. Biochem. 2006 97 1 84 97 10.1002/jcb.20546 16088956
    [Google Scholar]
  171. Miyamoto C. Matsumoto T. Sakimura K. Shindo H. Osteogenic protein-1 with transforming growth factor-β1: Potent Inducer of chondrogenesis of synovial mesenchymal stem cells in vitro. J. Orthop. Sci. 2007 12 6 555 561 10.1007/s00776‑007‑1176‑4 18040638
    [Google Scholar]
  172. Koizumi K. Ebina K. Hart D.A. Synovial mesenchymal stem cells from osteo- or rheumatoid arthritis joints exhibit good potential for cartilage repair using a scaffold-free tissue engineering approach. Osteoarthritis Cartilage 2016 24 8 1413 1422 10.1016/j.joca.2016.03.006 26973329
    [Google Scholar]
  173. Enomoto T. Akagi R. Ogawa Y. Timing of intra-articular injection of synovial mesenchymal stem cells affects cartilage restoration in a partial thickness cartilage defect model in rats. Cartilage 2020 11 1 122 129 10.1177/1947603518786542 29989441
    [Google Scholar]
  174. Guo S.C. Tao S.C. Yin W.J. Qi X. Sheng J.G. Zhang C.Q. Exosomes from human synovial-derived mesenchymal stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head in the rat. Int. J. Biol. Sci. 2016 12 10 1262 1272 10.7150/ijbs.16150 27766040
    [Google Scholar]
  175. Kim Y.S. Koh Y.G. Comparative matched-pair analysis of open-wedge high tibial osteotomy with versus without an injection of adipose-derived mesenchymal stem cells for varus knee osteoarthritis: Clinical and second-look arthroscopic results. Am. J. Sports Med. 2018 46 11 2669 2677 10.1177/0363546518785973 30080423
    [Google Scholar]
  176. Manferdini C. Maumus M. Gabusi E. Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. Arthritis Rheum. 2013 65 5 1271 1281 10.1002/art.37908 23613363
    [Google Scholar]
  177. Damia E. Chicharro D. Lopez S. Adipose-derived mesenchymal stem cells: Are they a good therapeutic strategy for osteoarthritis? Int. J. Mol. Sci. 2018 19 7 1926 10.3390/ijms19071926 29966351
    [Google Scholar]
  178. Tofiño-Vian M. Guillén M.I. Pérez del Caz M.D. Castejón M.A. Alcaraz M.J. Extracellular vesicles from adipose‐derived mesenchymal stem cells downregulate senescence features in osteoarthritic osteoblasts. Oxid. Med. Cell. Longev. 2017 2017 1 7197598 10.1155/2017/7197598 29230269
    [Google Scholar]
  179. Tofiño-Vian M. Guillén M.I. Pérez del Caz M.D. Silvestre A. Alcaraz M.J. Microvesicles from human adipose tissue-derived mesenchymal stem cells as a new protective strategy in osteoarthritic chondrocytes. Cell. Physiol. Biochem. 2018 47 1 11 25 10.1159/000489739 29763932
    [Google Scholar]
  180. Woo C.H. Kim H.K. Jung G.Y. Small extracellular vesicles from human adipose‐derived stem cells attenuate cartilage degeneration. J. Extracell. Vesicles 2020 9 1 1735249 10.1080/20013078.2020.1735249 32284824
    [Google Scholar]
  181. Zhao C. Chen J.Y. Peng W.M. Yuan B. Bi Q. Xu Y.J. Exosomes from adipose derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR 145 and miR 221. Mol. Med. Rep. 2020 21 4 1881 1889 10.3892/mmr.2020.10982 32319611
    [Google Scholar]
  182. Hwang N. Elisseeff J. Application of stem cells for articular cartilage regeneration. J. Knee Surg. 2009 22 1 60 71 10.1055/s‑0030‑1247728 19216354
    [Google Scholar]
  183. Mamidi M.K. Das A.K. Zakaria Z. Bhonde R. Mesenchymal stromal cells for cartilage repair in osteoarthritis. Osteoarthritis Cartilage 2016 24 8 1307 1316 10.1016/j.joca.2016.03.003 26973328
    [Google Scholar]
  184. Gibson J.D. O’Sullivan M.B. Alaee F. Regeneration of articular cartilage by human ESC-derived mesenchymal progenitors treated sequentially with BMP-2 and Wnt5a. Stem Cells Transl. Med. 2017 6 1 40 50 10.5966/sctm.2016‑0020 28170184
    [Google Scholar]
  185. Zhang S. Chu W.C. Lai R.C. Lim S.K. Hui J.H.P. Toh W.S. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage 2016 24 12 2135 2140 10.1016/j.joca.2016.06.022 27390028
    [Google Scholar]
  186. Wang Y. Yu D. Liu Z. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res. Ther. 2017 8 1 189 10.1186/s13287‑017‑0632‑0 28807034
    [Google Scholar]
  187. Zhang S. Teo K.Y.W. Chuah S.J. Lai R.C. Lim S.K. Toh W.S. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials 2019 200 35 47 10.1016/j.biomaterials.2019.02.006 30771585
    [Google Scholar]
  188. Zavatti M. Beretti F. Casciaro F. Bertucci E. Maraldi T. Comparison of the therapeutic effect of amniotic fluid stem cells and their exosomes on monoiodoacetate‐induced animal model of osteoarthritis. Biofactors 2020 46 1 106 117 10.1002/biof.1576 31625201
    [Google Scholar]
  189. Liu Y. Zeng Y. Si H.B. Tang L. Xie H.Q. Shen B. Exosomes] derived from human urine–derived stem cells overexpressing] miR-140-5p alleviate knee osteoarthritis through downregulation of VEGFA in a rat model. Am. J. Sports Med. 2022 50 4 1088 1105 10.1177/03635465221073991 35179989
    [Google Scholar]
  190. Kang L. Wang J. Zhang Y. Kou Z. Gao S. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 2009 5 2 135 138 10.1016/j.stem.2009.07.001 19631602
    [Google Scholar]
  191. Hirschi K.K. Li S. Roy K. Induced pluripotent stem cells for regenerative medicine. Annu. Rev. Biomed. Eng. 2014 16 1 277 294 10.1146/annurev‑bioeng‑071813‑105108 24905879
    [Google Scholar]
  192. Tracy S.A. Ahmed A. Tigges J.C. A comparison of clinically relevant sources of mesenchymal stem cell-derived exosomes: Bone marrow and amniotic fluid. J. Pediatr. Surg. 2019 54 1 86 90 10.1016/j.jpedsurg.2018.10.020 30361074
    [Google Scholar]
  193. Yan L. Wu X. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity. Cell Biol. Toxicol. 2020 36 2 165 178 10.1007/s10565‑019‑09504‑5 31820164
    [Google Scholar]
  194. Taylor P.R. Martinez-Pomares L. Stacey M. Lin H-H. Brown G.D. Gordon S. Macrophage receptors and immune recognition. Annu. Rev. Immunol. 2005 23 1 901 944 10.1146/annurev.immunol.23.021704.115816 15771589
    [Google Scholar]
  195. Sun Y. Zuo Z. Kuang Y. An emerging target in the battle against osteoarthritis: Macrophage polarization. Int. J. Mol. Sci. 2020 21 22 8513 10.3390/ijms21228513 33198196
    [Google Scholar]
  196. Miao X. Leng X. Zhang Q. The current state of nanoparticle-induced macrophage polarization and reprogramming research. Int. J. Mol. Sci. 2017 18 2 336 10.3390/ijms18020336 28178185
    [Google Scholar]
  197. Topoluk N. Steckbeck K. Siatkowski S. Burnikel B. Tokish J. Mercuri J. Amniotic mesenchymal stem cells mitigate osteoarthritis progression in a synovial macrophage‐mediated in vitro] explant coculture model. J. Tissue Eng. Regen. Med. 2018 12 4 1097 1110 10.1002/term.2610 29131526
    [Google Scholar]
  198. Wang R. Xu B. TGF-β1-modified MSC-derived exosomal miR-135b attenuates cartilage injury via promoting M2 synovial macrophage polarization by targeting MAPK6. Cell Tissue Res. 2021 384 1 113 127 10.1007/s00441‑020‑03319‑1 33404840
    [Google Scholar]
  199. Goldring S.R. Goldring M.B. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage–bone crosstalk. Nat. Rev. Rheumatol. 2016 12 11 632 644 10.1038/nrrheum.2016.148 27652499
    [Google Scholar]
  200. Chen L. Yao F. Wang T. Horizontal fissuring at the osteochondral interface: A novel and unique pathological feature in patients with obesity-related osteoarthritis. Ann. Rheum. Dis. 2020 79 6 811 818 10.1136/annrheumdis‑2020‑216942 32269059
    [Google Scholar]
  201. Yuan X.L. Meng H.Y. Wang Y.C. Bone-cartilage interface crosstalk in osteoarthritis: Potential pathways and future therapeutic strategies. Osteoarthritis Cartilage 2014 22 8 1077 1089 10.1016/j.joca.2014.05.023 24928319
    [Google Scholar]
  202. Burr D.B. Gallant M.A. Bone remodelling in osteoarthritis. Nat. Rev. Rheumatol. 2012 8 11 665 673 10.1038/nrrheum.2012.130 22868925
    [Google Scholar]
  203. Wu X. Crawford R. Xiao Y. Mao X. Prasadam I. Osteoarthritic subchondral bone release exosomes that promote cartilage degeneration. Cells 2021 10 2 251 10.3390/cells10020251 33525381
    [Google Scholar]
  204. Liu J. Wu X. Lu J. Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression. Nat. Aging 2021 1 4 368 384 10.1038/s43587‑021‑00050‑6 37117596
    [Google Scholar]
  205. Lu J. Zhang Y. Yang X. Zhao H. Harnessing exosomes as cutting-edge drug delivery systems for revolutionary osteoarthritis therapy. Biomed. Pharmacother. 2023 165 115135 10.1016/j.biopha.2023.115135 37453195
    [Google Scholar]
  206. Duan L. Xu X. Xu L. Exosome-mediated drug delivery for cell-free therapy of osteoarthritis. Curr. Med. Chem. 2021 28 31 6458 6483 10.2174/1875533XMTExENjQg4 33213308
    [Google Scholar]
  207. Liang Y. Xu X. Li X. Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy. ACS Appl. Mater. Interfaces 2020 12 33 36938 36947 10.1021/acsami.0c10458 32814390
    [Google Scholar]
  208. Xu X. Liang Y. Li X. Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration. Biomaterials 2021 269 120539 10.1016/j.biomaterials.2020.120539 33243424
    [Google Scholar]
  209. Wang J. Li X. Wang S. Cui J. Ren X. Su J. Bone‐targeted exosomes: Strategies and applications. Adv. Healthc. Mater. 2023 12 18 2203361 10.1002/adhm.202203361 36881547
    [Google Scholar]
  210. Lin Z. Xiong Y. Meng W. Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant. Bioact. Mater. 2022 13 300 311 10.1016/j.bioactmat.2021.10.042 35224310
    [Google Scholar]
  211. Mi B. Chen L. Xiong Y. Osteoblast/osteoclast and immune cocktail therapy of an exosome/drug delivery multifunctional hydrogel accelerates fracture repair. ACS Nano 2022 16 1 771 782 10.1021/acsnano.1c08284 34979087
    [Google Scholar]
  212. Liang Y. Xu X. Xu L. Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment. Theranostics 2022 12 11 4866 4878 10.7150/thno.69368 35836795
    [Google Scholar]
  213. Liang Y. Duan L. Lu J. Xia J. Engineering exosomes for targeted drug delivery. Theranostics 2021 11 7 3183 3195 10.7150/thno.52570 33537081
    [Google Scholar]
  214. Gao Y. Yuan Z. Yuan X. Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration. Bioact. Mater. 2022 14 377 388 10.1016/j.bioactmat.2022.01.041 35386817
    [Google Scholar]
  215. Liu W. Li L. Rong Y. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater. 2020 103 196 212 10.1016/j.actbio.2019.12.020 31857259
    [Google Scholar]
  216. Song M. Han L. Chen F. Adipocyte-derived exosomes carrying sonic hedgehog mediate M1 macrophage polarization-induced insulin resistance via Ptch and PI3K pathways. Cell. Physiol. Biochem. 2018 48 4 1416 1432 10.1159/000492252 30064125
    [Google Scholar]
  217. Wang Z. Maruyama K. Sakisaka Y. Cyclic stretch force induces periodontal ligament cells to secrete exosomes that suppress IL-1β production through the inhibition of the NF-κB signaling pathway in macrophages. Front. Immunol. 2019 10 1310 10.3389/fimmu.2019.01310 31281309
    [Google Scholar]
  218. Bhimani R. Singh P. Bhimani F. Rapidly progressive hip disease - A rare entity in Korean population. Int. J. Surg. Case Rep. 2018 53 486 489 10.1016/j.ijscr.2018.11.055 30567076
    [Google Scholar]
  219. Lipina M. Makarov M. Makarov S. Novikov A. The degree of cartilage degradation assessed by serum biomarker levels changes after arthroscopic knee synovectomy in rheumatoid arthritis patients. Int. Orthop. 2017 41 11 2259 2264 10.1007/s00264‑017‑3634‑8 28889180
    [Google Scholar]
  220. Zhang W. Qi L. Chen R. Circular RNAs in osteoarthritis: Indispensable regulators and novel strategies in clinical implications. Arthritis Res. Ther. 2021 23 1 23 10.1186/s13075‑021‑02420‑2 33436088
    [Google Scholar]
  221. Mao X. Cao Y. Guo Z. Wang L. Xiang C. Biological roles and therapeutic potential of circular RNAs in osteoarthritis. Mol. Ther. Nucleic Acids 2021 24 856 867 10.1016/j.omtn.2021.04.006 34026329
    [Google Scholar]
  222. Yang J. Zhang Y.S. Yue K. Khademhosseini A. Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater. 2017 57 1 25 10.1016/j.actbio.2017.01.036 28088667
    [Google Scholar]
  223. Khorshidi S. Karkhaneh A. A review on gradient hydrogel/fiber scaffolds for osteochondral regeneration. J. Tissue Eng. Regen. Med. 2018 12 4 e1974 e1990 10.1002/term.2628 29243352
    [Google Scholar]
  224. Chen Z. Zhang Q. Li H. Wei Q. Zhao X. Chen F. Elastin-like polypeptide modified silk fibroin porous scaffold promotes osteochondral repair. Bioact. Mater. 2021 6 3 589 601 10.1016/j.bioactmat.2020.09.003 33005824
    [Google Scholar]
  225. Bei H.P. Hung P.M. Yeung H.L. Wang S. Zhao X. Bone‐a‐petite: Engineering exosomes towards bone, osteochondral, and cartilage repair. Small 2021 17 50 2101741 10.1002/smll.202101741 34288410
    [Google Scholar]
  226. Taylor D.L. in het Panhuis M. Self‐healing hydrogels. Adv. Mater. 2016 28 41 9060 9093 10.1002/adma.201601613 27488822
    [Google Scholar]
  227. Zhao Z. Fang R. Rong Q. Liu M. Bioinspired nanocomposite hydrogels with highly ordered structures. Adv. Mater. 2017 29 45 1703045 10.1002/adma.201703045 29059482
    [Google Scholar]
  228. Murphy M.P. Koepke L.S. Lopez M.T. Articular cartilage regeneration by activated skeletal stem cells. Nat. Med. 2020 26 10 1583 1592 10.1038/s41591‑020‑1013‑2 32807933
    [Google Scholar]
  229. Nikhil A. Kumar A. Evaluating potential of tissue‐engineered cryogels and chondrocyte derived exosomes in articular cartilage repair. Biotechnol. Bioeng. 2022 119 2 605 625 10.1002/bit.27982 34723385
    [Google Scholar]
  230. Wei F. Li M. Crawford R. Zhou Y. Xiao Y. Exosome-integrated titanium oxide nanotubes for targeted bone regeneration. Acta Biomater. 2019 86 480 492 10.1016/j.actbio.2019.01.006 30630122
    [Google Scholar]
  231. Swanson W.B. Zhang Z. Xiu K. Scaffolds with controlled release of pro-mineralization exosomes to promote craniofacial bone healing without cell transplantation. Acta Biomater. 2020 118 215 232 10.1016/j.actbio.2020.09.052 33065285
    [Google Scholar]
  232. Fan W.J. Liu D. Pan L.Y. Exosomes in osteoarthritis: Updated insights on pathogenesis, diagnosis, and treatment. Front. Cell Dev. Biol. 2022 10 949690 10.3389/fcell.2022.949690 35959489
    [Google Scholar]
  233. Zhang F.X. Liu P. Ding W. Injectable mussel‐inspired] highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration. Biomaterials 2021 278 121169 10.1016/j.biomaterials.2021.121169 34626937
    [Google Scholar]
  234. Xu H. Xu B. BMSC‐derived exosomes ameliorate osteoarthritis by inhibiting pyroptosis of cartilage via delivering miR‐326 targeting HDAC3 and STAT1//NF‐κB p65 to chondrocytes. Mediators Inflamm. 2021 2021 1 9972805 10.1155/2021/9972805 34764819
    [Google Scholar]
  235. Jin Y. Xu M. Zhu H. Therapeutic effects of bone marrow mesenchymal stem cells‐derived exosomes on osteoarthritis. J. Cell. Mol. Med. 2021 25 19 9281 9294 10.1111/jcmm.16860 34448527
    [Google Scholar]
  236. Jiang K. Jiang T. Chen Y. Mao X. Mesenchymal stem cell‐derived exosomes modulate chondrocyte glutamine metabolism to alleviate osteoarthritis progression. Mediators Inflamm. 2021 2021 1 2979124 10.1155/2021/2979124 34992497
    [Google Scholar]
  237. Wang Y. Fan A. Lu L. Exosome modification to better alleviates endoplasmic reticulum stress induced chondrocyte apoptosis and osteoarthritis. Biochem. Pharmacol. 2022 206 115343 10.1016/j.bcp.2022.115343 36370754
    [Google Scholar]
  238. Yin Z. Qin C. Pan S. Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis. Mater. Today Bio 2023 23 100813 10.1016/j.mtbio.2023.100813 37822452
    [Google Scholar]
  239. Zhao J. Sun Y. Sheng X. Hypoxia-treated adipose mesenchymal stem cell-derived exosomes attenuate lumbar facet joint osteoarthritis. Mol. Med. 2023 29 1 120 10.1186/s10020‑023‑00709‑3 37670256
    [Google Scholar]
  240. Chen X. Tian B. Wang Y. Zheng J. Kang X. Potential and challenges of utilizing exosomes in osteoarthritis therapy.(Review) Int. J. Mol. Med. 2025 55 3 43 10.3892/ijmm.2025.5484 39791222
    [Google Scholar]
  241. Fu Y. Cui S. Zhou Y. Qiu L. Dental pulp stem cell-derived exosomes alleviate mice knee osteoarthritis by inhibiting TRPV4-mediated osteoclast activation. Int. J. Mol. Sci. 2023 24 5 4926 10.3390/ijms24054926 36902356
    [Google Scholar]
  242. Meng C. Na Y. Han C. Exosomal miR-429 derived from adipose-derived stem cells ameliorated chondral injury in osteoarthritis via autophagy by targeting FEZ2. Int. Immunopharmacol. 2023 120 110315 10.1016/j.intimp.2023.110315 37245297
    [Google Scholar]
  243. Yang H. Zhou Y. Ying B. Dong X. Qian Q. Gao S. Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models. Stem Cells Transl. Med. 2024 13 8 803 811 10.1093/stcltm/szae031 38913985
    [Google Scholar]
  244. Huang C. Zhao Y. Lin S. Characterization of human placenta-derived exosome (pExo) as a potential osteoarthritis disease modifying therapeutic. Arthritis Res. Ther. 2023 25 1 229 10.1186/s13075‑023‑03219‑z 38017556
    [Google Scholar]
  245. Zhao S. Xiu G. Wang J. Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis. J. Nanobiotechnology 2023 21 1 341 10.1186/s12951‑023‑02086‑9 37736726
    [Google Scholar]
  246. Yang L. Li W. Zhao Y. Shang L. Magnetic polysaccharide mesenchymal stem cells exosomes delivery microcarriers for synergistic therapy of osteoarthritis. ACS Nano 2024 18 31 20101 20110 10.1021/acsnano.4c01406 39039744
    [Google Scholar]
  247. Ma T. Xu G. Gao T. Engineered exosomes with ATF5-modified mRNA loaded in injectable thermogels alleviate osteoarthritis by targeting the mitochondrial unfolded protein response. ACS Appl. Mater. Interfaces 2024 16 17 21383 21399 10.1021/acsami.3c17209 38626424
    [Google Scholar]
  248. Zhang Y. Wang X. Chen J. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis. J. Nanobiotechnology 2022 20 1 56 10.1186/s12951‑022‑01245‑8 35093078
    [Google Scholar]
  249. Lou C. Jiang H. Lin Z. MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6. J. Nanobiotechnology 2023 21 1 486 10.1186/s12951‑023‑02264‑9 38105181
    [Google Scholar]
  250. Meng S. Tang C. Deng M. Tropoelastin-pretreated exosomes from adipose-derived stem cells improve the synthesis of cartilage matrix and alleviate osteoarthritis. J. Funct. Biomater. 2023 14 4 203 10.3390/jfb14040203 37103293
    [Google Scholar]
  251. Wang S. Jiang W. Lv S. Human umbilical cord mesenchymal stem cells-derived exosomes exert anti-inflammatory effects on osteoarthritis chondrocytes. Aging (Albany NY) 2023 15 18 9544 9560 10.18632/aging.205034 37724890
    [Google Scholar]
  252. Chen J. Ni X. Yang J. Cartilage stem/progenitor cells‐derived exosomes facilitate knee cartilage repair in a subacute osteoarthritis rat model. J. Cell. Mol. Med. 2024 28 8 e18327 10.1111/jcmm.18327 38661437
    [Google Scholar]
  253. Patel A.A. Mohamed A.H. Rizaev J. Application of mesenchymal stem cells derived from the umbilical cord or Wharton’s jelly and their extracellular vesicles in the treatment of various diseases. Tissue Cell 2024 89 102415 10.1016/j.tice.2024.102415 38851032
    [Google Scholar]
  254. Xie W. Su W. Xia H. Wang Z. Su C. Su B. Synovial fluid microRNA-210 as a potential biomarker for early prediction of osteoarthritis. BioMed Res. Int. 2019 2019 1 1 4 10.1155/2019/7165406 31467907
    [Google Scholar]
  255. Miao C. Zhou W. Wang X. Fang J. The research progress of exosomes in osteoarthritis, with particular emphasis on the mediating roles of miRNAs and lncRNAs. Front. Pharmacol. 2021 12 685623 10.3389/fphar.2021.685623 34093208
    [Google Scholar]
  256. Murata K. Yoshitomi H. Tanida S. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res. Ther. 2010 12 3 R86 10.1186/ar3013 20470394
    [Google Scholar]
  257. Qiu M. Liu D. Fu Q. MiR-129-5p shuttled by human synovial mesenchymal stem cell-derived exosomes relieves IL-1β induced osteoarthritis via targeting HMGB1. Life Sci. 2021 269 118987 10.1016/j.lfs.2020.118987 33417958
    [Google Scholar]
  258. Kawakami K. Fujita Y. Matsuda Y. Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer. BMC Cancer 2017 17 1 316 10.1186/s12885‑017‑3301‑x 28476099
    [Google Scholar]
  259. Rabinowits G. Gerçel-Taylor C. Day J.M. Taylor D.D. Kloecker G.H. Exosomal microRNA: A diagnostic marker for lung cancer. Clin. Lung Cancer 2009 10 1 42 46 10.3816/CLC.2009.n.006 19289371
    [Google Scholar]
  260. Lv L.L. Cao Y.H. Ni H.F. MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. Am. J. Physiol. Renal Physiol. 2013 305 8 F1220 F1227 10.1152/ajprenal.00148.2013 23946286
    [Google Scholar]
  261. Song J. Kim D. Han J. Kim Y. Lee M. Jin E.J. PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin. Exp. Med. 2015 15 1 121 126 10.1007/s10238‑013‑0271‑4 24722995
    [Google Scholar]
  262. van Spil W.E. DeGroot J. Lems W.F. Oostveen J.C.M. Lafeber F.P.J.G. Serum and urinary biochemical markers for knee and hip-osteoarthritis: A systematic review applying the consensus BIPED criteria. Osteoarthritis Cartilage 2010 18 5 605 612 10.1016/j.joca.2010.01.012 20175979
    [Google Scholar]
  263. Charni N. Juillet F. Garnero P. Urinary type II collagen helical peptide (HELIX‐II) as a new biochemical marker of cartilage degradation in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2005 52 4 1081 1090 10.1002/art.20930 15818703
    [Google Scholar]
  264. Garnero P. Charni N. Juillet F. Conrozier T. Vignon E. Increased urinary type II collagen helical and C telopeptide levels are independently associated with a rapidly destructive hip osteoarthritis. Ann. Rheum. Dis. 2006 65 12 1639 1644 10.1136/ard.2006.052621 16569684
    [Google Scholar]
  265. van der Lubbe N. Jansen P.M. Salih M. The phosphorylated sodium chloride cotransporter in urinary exosomes is superior to prostasin as a marker for aldosteronism. Hypertension 2012 60 3 741 748 10.1161/HYPERTENSIONAHA.112.198135 22851731
    [Google Scholar]
  266. Yazarlou F. Modarressi M.H. Mowla S.J. Urinary exosomal expression of long non-coding RNAs as diagnostic marker in bladder cancer. Cancer Manag. Res. 2018 10 6357 6365 10.2147/CMAR.S186108 30568497
    [Google Scholar]
  267. Street J.M. Koritzinsky E.H. Glispie D.M. Star R.A. Yuen P.S. Urine exosomes: An emerging trove of biomarkers. Adv. Clin. Chem. 2017 78 103 122 10.1016/bs.acc.2016.07.003 28057185
    [Google Scholar]
  268. H Rashed M Exosomes: From garbage bins to promising therapeutic targets. Int. J. Mol. Sci. 2017 18 3 538 10.3390/ijms18030538 28257101
    [Google Scholar]
  269. Gernapudi R. Yao Y. Zhang Y. Targeting exosomes from preadipocytes inhibits preadipocyte to cancer stem cell signaling in early-stage breast cancer. Breast Cancer Res. Treat. 2015 150 3 685 695 10.1007/s10549‑015‑3326‑2 25783182
    [Google Scholar]
  270. Hornick N.I. Doron B. Abdelhamed S. AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB. Sci. Signal. 2016 9 444 ra88 ra8 10.1126/scisignal.aaf2797 27601730
    [Google Scholar]
  271. Mak J. Jablonski C.L. Leonard C.A. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci. Rep. 2016 6 1 23076 10.1038/srep23076 26983696
    [Google Scholar]
  272. Chen P. Ruan A. Zhou J. Extraction and identification of synovial tissue-derived exosomes by different separation techniques. J. Orthop. Surg. Res. 2020 15 1 97 10.1186/s13018‑020‑01604‑x 32151262
    [Google Scholar]
  273. Liu X. Yang Y. Li Y. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale 2017 9 13 4430 4438 10.1039/C7NR00352H 28300264
    [Google Scholar]
  274. Wang C. Wang M. Xu T. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics 2019 9 1 65 76 10.7150/thno.29766 30662554
    [Google Scholar]
  275. Shi Q. Qian Z. Liu D. GMSC-derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Front. Physiol. 2017 8 904 10.3389/fphys.2017.00904 29163228
    [Google Scholar]
  276. Han C. Zhou J. Liang C. Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair. Biomater. Sci. 2019 7 7 2920 2933 10.1039/C9BM00101H 31090763
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128412201251125100451
Loading
/content/journals/cpd/10.2174/0113816128412201251125100451
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test