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2000
Volume 21, Issue 5
  • ISSN: 1570-1646
  • E-ISSN: 1875-6247

Abstract

Background

Osteoarthritis (OA) is one of the leading causes of pain and disability. Metabolomics is a recent approach to identifying moieties that can be used in diagnosis, prognosis, and as biomarkers. The articular fluid in OA witnesses its pathophysiology directly. Identifying differential metabolites and biological pathways associated with them can provide in-depth mechanisms and identify biomarkers.

Aim

In the present study, synovial fluid of confirmed OA patients (n=17) and matched healthy controls (n=21) was investigated for differential metabolites using untargeted metabolomics.

Methods

The distribution of the samples was observed using multidimensional PCA. The signaling pathways associated with metabolites were obtained by pathway enrichment analysis, and a correlation analysis of differential metabolites was performed to identify common and significant metabolites.

Results

A total of 16 upregulated and 23 downregulated metabolites (log2foldchange >0.5, <0.05) were identified by differential analysis. The essential amino acid, arginine, was recognized as the most significant metabolite present in most of the identified deregulated pathways. The pathways, arginine, and proline metabolisms, and mTOR, were found to be deregulated strongly in the present study.

Conclusion

These metabolites and their associated pathways can be beneficial for the diagnosis and treatment of osteoarthritis in clinical settings after further validation in large cohorts.

© 2024 Bentham Science Publishers
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2025-09-13

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References

  1. ChuC.R. MillisM.B. OlsonS.A. Osteoarthritis: From palliation to prevention: AOA critical issues.J. Bone Joint Surg. Am.20149615e13010.2106/JBJS.M.0120925100783
     [Google Scholar]
  2. BarbourK.E. HelmickC.G. TheisK.A. MurphyL.B. HootmanJ.M. BradyT.J. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation--United States, 2010-2012.MMWR Morb Mortal Wkly Rep201362448697324196662
     [Google Scholar]
  3. BlagojevicM. JinksC. JefferyA. JordanK.P Risk factors for onset of osteoarthritis of the knee in older adults: A systematic review and meta-analysis.Osteoarthritis Cartilage2010181243310.1016/j.joca.2009.08.010.
     [Google Scholar]
  4. JiS. LiuL. LiJ. ZhaoG. CaiY. DongY. WangJ. WuS. Prevalence and factors associated with knee osteoarthritis among middle-aged and elderly individuals in rural Tianjin: A population-based cross-sectional study.J Orthop Surg Res.20231826610.1186/s13018‑023‑03742‑4.
     [Google Scholar]
  5. ZhangJ. SongL. WeiJ. ZhangA. DongH. WenH. LuoJ. LiuG. Prevalence of and risk factors for the occurrence of symptomatic osteoarthritis in rural regions of Shanxi Province, China.Int. J. Rheum. Dis.201619878178910.1111/1756‑185X.1247025267183
     [Google Scholar]
  6. BeroS.A. MudaA.K. ChooY.H. MudaN.A. PratamaS.F. Weighted Tanimoto coefficient for 3D molecule structure similarity measurement.arXiv201810.48550/arXiv.1806.05237.
     [Google Scholar]
  7. LiJ.T. ZengN. YanZ.P. LiaoT. NiG.X. A review of applications of metabolomics in osteoarthritis.Clin. Rheumatol.20214072569257910.1007/s10067‑020‑05511‑833219452
     [Google Scholar]
  8. HuS. ZhangC. NiL. HuangC. ChenD. ShiK. JinH. ZhangK. LiY. XieL. Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy.Cell Death Dis202011648110.1038/s41419‑020‑2680‑0.
     [Google Scholar]
  9. HeA. NingY. WenY. CaiY. XuK. HanJ. LiuL. DuY. LiangX. LiP. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage.Bone Joint Res20187534335010.1302/2046‑3758.75.BJR‑2017‑0284.R1.
     [Google Scholar]
  10. BurgerM.G. SteinitzA. GeurtsJ. PippengerB.E. SchaeferD.J. MartinI. BarberoA. PelttariK. Ascorbic acid attenuates senescence of human osteoarthritic osteoblasts.Int J Mol Sci20171812251710.3390/ijms18122517
     [Google Scholar]
  11. RockelJ.S. KapoorM.J.M. The Metabolome and Osteoarthritis: Possible contributions to symptoms and pathology.Metabolites2018849210.3390/metabo8040092
     [Google Scholar]
  12. ShowiheenS.A.A. SunA.R. WuX. CrawfordR. XiaoY. WellardR.M. PrasadamI. Application of metabolomics to osteoarthritis: From basic science to the clinical approach.Curr. Rheumatol. Rep.20192162610.1007/s11926‑019‑0827‑831062102
     [Google Scholar]
  13. ZhangW. LikhodiiS. ZhangY. Aref-EshghiE. HarperP.E. RandellE. GreenR. MartinG. FureyA. SunG. RahmanP. ZhaiG. Classification of osteoarthritis phenotypes by metabolomics analysis.BMJ Open2014411e00628610.1136/bmjopen‑2014‑00628625410606
     [Google Scholar]
  14. AdamsS.B.Jr SettonL.A. NettlesD.L. The role of metabolomics in osteoarthritis research.J. Am. Acad. Orthop. Surg.2013211636410.5435/JAAOS‑21‑01‑6323281473
     [Google Scholar]
  15. AltmanR. AlarconG. AppelrouthD. BlochD. BorensteinD. BrandtK. BrownC. CookeT. DanielW. FeldmanD. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip.Arthritis Rheum19913455051410.1002/art.1780340502
     [Google Scholar]
  16. AltmanR. AschE. BlochD. BoleG. BorensteinD. BrandtK. ChristyW. CookeT. GreenwaldR. HochbergM. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.Arthritis Rheum198629810394910.1002/art.1780290816
     [Google Scholar]
  17. HuT. ZhangW. FanZ. SunG. LikhodiS. RandellE. ZhaiG. Metabolomics differential correlation network analysis of Osteoarthritis.Pacific Symposium on Biocomputing (PSB)201612013110.1142/9789814749411_0012
     [Google Scholar]
  18. BoudonckK.J. MitchellM.W. NémetL. KeresztesL. NyskaA. ShinarD. RosenstockM. Discovery of metabolomics biomarkers for early detection of nephrotoxicity.Toxicol. Pathol.200937328029210.1177/019262330933299219380839
     [Google Scholar]
  19. ZhengK. ShenN. ChenH. NiS. ZhangT. HuM. WangJ. SunL. YangX. Global and targeted metabolomics of synovial fluid discovers special osteoarthritis metabolites.J. Orthop. Res.20173591973198110.1002/jor.2348228439964
     [Google Scholar]
  20. Bay-JensenA.C. BihletA. ByrjalsenI. AndersenJ.R. RiisB.J. ChristiansenC. MichaelisM. GuehringH. LadelC. KarsdalM.A. Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis.Sci. Rep.2021111658310.1038/s41598‑021‑86064‑x33753821
     [Google Scholar]
  21. LuW. SuX. KleinM.S. LewisI.A. FiehnO. RabinowitzJ.D. Metabolite measurement: Pitfalls to avoid and practices to follow.Annu. Rev. Biochem.201786127730410.1146/annurev‑biochem‑061516‑04495228654323
     [Google Scholar]
  22. TootsiK. VilbaK. MärtsonA. KalsJ. PaapstelK. ZilmerM. Metabolomic signature of amino acids, biogenic amines and lipids in blood serum of patients with severe osteoarthritis.Metabolites202010832310.3390/metabo1008032332784380
     [Google Scholar]
  23. WuG. Functional amino acids in growth, reproduction, and health.Adv. Nutr.201011313710.3945/an.110.100822043449
     [Google Scholar]
  24. MorrisS.M.Jr Arginine: Beyond protein.Am. J. Clin. Nutr.2006832508S512S10.1093/ajcn/83.2.508S16470022
     [Google Scholar]
  25. WinterG. ToddC.D. TrovatoM. ForlaniG. FunckD. Physiological implications of arginine metabolism in plants.Front. Plant Sci.2015653410.3389/fpls.2015.0053426284079
     [Google Scholar]
  26. PhangJ.M. Proline metabolism in cell regulation and cancer biology: Recent advances and hypotheses.Antioxid. Redox Signal.201930463564910.1089/ars.2017.735028990419
     [Google Scholar]
  27. MorrisS.M.Jr Arginine metabolism revisited.J. Nutr.2016146122579S2586S10.3945/jn.115.22662127934648
     [Google Scholar]
  28. PhangJ.M. LiuW. HancockC.N. FischerJ.W. Proline metabolism and cancer.Curr. Opin. Clin. Nutr. Metab. Care2015181717710.1097/MCO.000000000000012125474014
     [Google Scholar]
  29. LiY. XiaoW. LuoW. ZengC. DengZ. RenW. WuG. LeiG. Alterations of amino acid metabolism in osteoarthritis: Its implications for nutrition and health.Amino Acids201648490791410.1007/s00726‑015‑2168‑x26767374
     [Google Scholar]
  30. ChenR. HanS. LiuX. WangK. ZhouY. YangC. ZhangX. Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.20181085546210.1016/j.jchromb.2018.03.04729631251
     [Google Scholar]
  31. CarlsonA.K. RawleR.A. AdamsE. GreenwoodM.C. BothnerB. JuneR.K. Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers.Biochem. Biophys. Res. Commun.2018499218218810.1016/j.bbrc.2018.03.11729551687
     [Google Scholar]
  32. EngelmanJ.A. LuoJ. CantleyL.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.Nat. Rev. Genet.20067860661910.1038/nrg187916847462
     [Google Scholar]
  33. TangF. WangY. HemmingsB.A. XueG. RüeggC. PKB/Akt-dependent regulation of inflammation in cancer.Semin Cancer Biol201848626910.1016/j.semcancer.2017.04.018.
     [Google Scholar]
  34. SunK. LuoJ. GuoJ. YaoX. JingX. GuoF. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: A narrative review.Osteoarthritis Cartilage202028440040910.1016/j.joca.2020.02.02732081707
     [Google Scholar]
  35. VasheghaniF. ZhangY. LiY.H. BlatiM. FahmiH. LussierB. RoughleyP. LagaresD. EndishaH. SaffarB. LajeunesseD. MarshallW.K. RampersaudY.R. MahomedN.N. GandhiR. PelletierJ.P. Martel-PelletierJ. KapoorM. PPARγ deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage.Ann. Rheum. Dis.201574356957810.1136/annrheumdis‑2014‑20574325573665
     [Google Scholar]
  36. XueJ.F. ShiZ.M. ZouJ. LiX.L. Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis.Biomed. Pharmacother.2017891252126110.1016/j.biopha.2017.01.13028320092
     [Google Scholar]
  37. BakerN. SohnJ. TuanR.S. Promotion of human mesenchymal stem cell osteogenesis by PI3-kinase/Akt signaling, and the influence of caveolin-1/cholesterol homeostasis.Stem Cell Res. Ther.20156123810.1186/s13287‑015‑0225‑826626726
     [Google Scholar]
  38. PalB. EndishaH. ZhangY. KapoorM. mTOR: A potential therapeutic target in osteoarthritis?Drugs R D.2015151273610.1007/s40268‑015‑0082‑z25688060
     [Google Scholar]
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Osteoarthritis: Insights into Potential Causes and Biomarkers from Articular Fluid Metabonomics
Curr. Proteomics 21, 293 (2024); https://doi.org/10.2174/0115701646310314240910082445
/content/journals/cp/10.2174/0115701646310314240910082445
/content/journals/cp/10.2174/0115701646310314240910082445
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  • Article Type:     Research Article
Keyword(s): Arginine; metabolism; metabolomics; mTOR signaling pathway; osteoarthritis; pathophysiology

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