Skip to content
2000
Volume 32, Issue 6
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Introduction

The etiology of acute Achilles tendon rupture (ATR) remains unclear. This study conducted a comprehensive case-control study of the proteome profile to gain insights into the potential pathogenesis of acute ATR and identify novel biomarkers.

Methods

Serum (iTRAQ) and urine (label-free proteomics) from 15 acute ATR patients and 15 healthy controls were analyzed. Significant differential expression was defined as ≥1.2-fold (serum) or ≥2-fold (urine) change with  < 0.05. Bioinformatics analyses (GO, KEGG, PPI) were performed.

Results

44 serum and 198 urine proteins were differentially expressed. Enriched pathways included immune response, metabolism, immune response, and redox regulation. protein-protein interaction analysis of the differentially expressed proteins ( < 0.05) highlighted abnormalities in major protein-protein interaction hubs, specifically pyruvate kinase (PKM), peroxiredoxin-1 (PRDX1), phosphoglycerate kinase 1 (PKG1), profilin-1, and apolipoprotein A-IV, observed in the serum and urine samples of acute ATR patients.

Discussion

Metabolic dysregulation may affect tendon structure/strength; redox imbalance could promote degeneration. Immune-related proteins may reflect injury responses. Glycolytic enzymes (PKM, PGK1) suggest disrupted energy metabolism.

Conclusion

Proteomic abnormalities in metabolism, immune, and redox pathways, along with key proteins (PKM, PRDX1, PGK1), may contribute to ATR pathogenesis, offering potential biomarkers warranting further validation.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ppl/10.2174/0109298665374669250627205138
2025-07-09
2026-01-02

  • From This Site

    /content/journals/ppl/10.2174/0109298665374669250627205138
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. JielileJ. BadalihanA. QianmanB. SatewaledeT. WuerliebiekeJ. KelamuM. JialihasiA. Clinical outcome of exercise therapy and early post-operative rehabilitation for treatment of neglected Achilles tendon rupture: A randomized study.Knee Surg. Sports Traumatol. Arthrosc.20162472148215510.1007/s00167‑015‑3598‑425894749
     [Google Scholar]
  2. JielileJ. SabirhaziG. HuG. ChenJ. AldyarhanK. ZheyikenJ. ZhaoQ. BaiJ. Novel surgical technique and early kinesiotherapy for acute Achilles tendon rupture.Foot Ankle Int.201233121119112710.3113/FAI.2012.111923199864
     [Google Scholar]
  3. MansfieldK. DopkeK. KoroneosZ. BonaddioV. AdeyemoA. AynardiM. Achilles tendon ruptures and repair in athletes—a review of sports-related achilles injuries and return to play.Curr. Rev. Musculoskelet. Med.202215535336110.1007/s12178‑022‑09774‑335804260
     [Google Scholar]
  4. AisaidingA. WangJ. MaimaitiR. JialihasiA. AibekR. QianmanB. ShawutaliN. BadelihanA. BahetiyaW. KubaiA. KelamuM. NuerdoulaY. MakemutibiekeE. BakytY. WuerliebiekeJ. JielileJ. A novel minimally invasive surgery combined with early exercise therapy promoting tendon regeneration in the treatment of spontaneous Achilles tendon rupture.Injury201849371271910.1016/j.injury.2017.10.04629153451
     [Google Scholar]
  5. BadalihanA. AihemaitiA. ShawutaliN. JielileJ. JialihasiA. TangkejieW. NuerdoulaY. SatewaledeT. HunapiyaB. NiyazebiekeH. HezibiekeH. ZhaoQ. BahetijiangA. KelamuM. QianmanB. Outcome of a one-stage tensile stress surgical technique and early postoperative rehabilitation in the treatment of neglected Achilles tendon rupture.J. Foot Ankle Surg.201554215315910.1053/j.jfas.2014.12.00225703445
     [Google Scholar]
  6. SodeJ. ObelN. HallasJ. LassenA. Use of fluroquinolone and risk of Achilles tendon rupture: A population-based cohort study.Eur. J. Clin. Pharmacol.200763549950310.1007/s00228‑007‑0265‑917334751
     [Google Scholar]
  7. van der LindenP.D. SturkenboomM.C.J.M. HeringsR.M.C. LeufkensH.M.G. RowlandsS. StrickerB.H.C. Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids.Arch. Intern. Med.2003163151801180710.1001/archinte.163.15.180112912715
     [Google Scholar]
  8. JiashareteJ.J. QianmanB. ShawutaliN. TuomilisiJ. BadelihanA. JialihasiA. Achilles Tendon Surgery.Tianjin, ChinaScience and Technology Press20199321050
     [Google Scholar]
  9. HorvathD. HorvathM. A case of nontraumatic simultaneous bilateral Achilles tendon rupture.J. Am. Assoc. Nurse Pract.2023351285385510.1097/JXX.000000000000090637335847
     [Google Scholar]
  10. HolmesG.B. LinJ. Etiologic factors associated with symptomatic achilles tendinopathy.Foot Ankle Int.2006271195295910.1177/10711007060270111517144959
     [Google Scholar]
  11. KannusP. JózsaL. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients.J. Bone Joint Surg. Am.199173101507152510.2106/00004623‑199173100‑000091748700
     [Google Scholar]
  12. ArnerO. LindholmA. OrellS.R. Histologic changes in subcutaneous rupture of the Achilles tendon; a study of 74 cases.Acta Chir. Scand.19591165-648449013660717
     [Google Scholar]
  13. JózsaL. KannusP. Histopathological findings in spontaneous tendon ruptures.Scand. J. Med. Sci. Sports19977211311810.1111/j.1600‑0838.1997.tb00127.x9211612
     [Google Scholar]
  14. JielileJ. AsilehanB. WupuerA. QianmanB. JialihasiA. TangkejieW. MaimaitiailiA. ShawutaliN. BadelhanA. NiyazebiekeH. AizeziA. AisaidingA. BakytY. AibekR. WuerliebiekeJ. Early ankle mobilization promotes healing in a rabbit model of achilles tendon rupture.Orthopedics2016391e117e12610.3928/01477447‑20160106‑0126821224
     [Google Scholar]
  15. RozanovaS. BarkovitsK. NikolovM. SchmidtC. UrlaubH. MarcusK. Quantitative mass spectrometry-based proteomics: An overview.Methods Mol. Biol.202122288511610.1007/978‑1‑0716‑1024‑4_833950486
     [Google Scholar]
  16. HanashS. Disease proteomics.Nature2003422692822623210.1038/nature0151412634796
     [Google Scholar]
  17. MeringC. HuynenM. JaeggiD. SchmidtS. BorkP. SnelB. STRING: A database of predicted functional associations between proteins.Nucleic Acids Res.200331125826110.1093/nar/gkg03412519996
     [Google Scholar]
  18. ZhangG. EzuraY. ChervonevaI. RobinsonP.S. BeasonD.P. CarineE.T. SoslowskyL.J. IozzoR.V. BirkD.E. Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development.J. Cell. Biochem.20069861436144910.1002/jcb.2077616518859
     [Google Scholar]
  19. RaspantiM. CongiuT. GuizzardiS. Structural aspects of the extracellular matrix of the tendon: An atomic force and scanning electron microscopy study.Arch. Histol. Cytol.2002651374310.1679/aohc.65.3712002609
     [Google Scholar]
  20. CaonI. ParnigoniA. KarousouE. Biochemistry of hyaluronan synthesis.Hyaluronan: Structure, Biology and BiotechnologyChamSpringer2023
     [Google Scholar]
  21. (a) GustavA. Influences of paratendinous innervation and non-neuronal substance P in tendinopathy: Studies on human tendon tissue and an experimental model of Achilles tendinopathy.2010Available from: http://umu.diva-portal.org/smash/get/diva2:349953/FULLTEXT01 (b) Qianman, B.; Jiasharete, T.; Badalihan, A.; Mamately, A.; Yeerbo, N.; Bahesutihan, Y.; Wupuer, A.; Aisaiding, A.; Wuerliebieke, J.; Jialihasi, A.; Li, P.; Jielile, J. iTRAQ-based proteomic analysis of spontaneous Achilles tendon rupture. J. Proteome Res., 2025, 24(1):65-76. http://dx.doi.org/10.1021/acs.jproteome.4c00357. Epub 2024 Nov 27. PMID: 39601082. (c) Qianman, B.; Wupuer, A.; Jiasharete, T.; Luo, B.; Nihemaiti, M.; Jielile, J. iTRAQ-based proteomics reveals potential markers and treatment pathways for acute Achilles tendon rupture. J. Orthop. Surg. Res., 2023, 18(1):852. http://dx.doi.org/10.1186/s13018-023-04346-8. PMID: 37946221; PMCID: PMC10636927.
  22. LeeB.E.J. LuoL. GrandfieldK. AndreiC.M. SchwarczH.P. Identification of collagen fibrils in cross sections of bone by electron energy loss spectroscopy (EELS).Micron201912410270610.1016/j.micron.2019.10270631255883
     [Google Scholar]
  23. DakinS.G. MartinezF.O. YappC. WellsG. OppermannU. DeanB.J.F. SmithR.D.J. WhewayK. WatkinsB. RocheL. CarrA.J. Inflammation activation and resolution in human tendon disease.Sci. Transl. Med.20157311311ra17310.1126/scitranslmed.aac426926511510
     [Google Scholar]
  24. SiesH. Oxidative eustress: On constant alert for redox homeostasis.Redox Biol.20214110186710.1016/j.redox.2021.10186733657525
     [Google Scholar]
  25. GuptaV. BamezaiR.N.K. Human pyruvate kinase M2: A multifunctional protein.Protein Sci.201019112031204410.1002/pro.50520857498
     [Google Scholar]
  26. BlakeC.C. RiceD.W. Phosphoglycerate kinase.Philos. Trans. R. Soc. Lond. B Biol. Sci.198129310639310410.1098/rstb.1981.00636115427
     [Google Scholar]
  27. FujiiH. MiwaS. Other erythrocyte enzyme deficiencies associated with non-haematological symptoms: Phosphoglycerate kinase and phosphofructokinase deficiency.Best Pract. Res. Clin. Haematol.200013114114810.1053/beha.1999.006210916683
     [Google Scholar]
  28. RaskindW.H. WijsmanE. PagonR.A. CoxT.C. BawdenM.J. MayB.K. BirdT.D. X-linked sideroblastic anemia and ataxia: Linkage to phosphoglycerate kinase at Xq13.Am. J. Hum. Genet.19914823353411671320
     [Google Scholar]
  29. GraceR.F. ZanellaA. NeufeldE.J. MortonD.H. EberS. YaishH. GladerB. Erythrocyte pyruvate kinase deficiency: 2015 status report.Am. J. Hematol.201590982583010.1002/ajh.2408826087744
     [Google Scholar]
  30. AnselmentB. BaerendD. MeyE. BuchnerJ. Weuster-BotzD. HaslbeckM. Experimental optimization of protein refolding with a genetic algorithm.Protein Sci.201019112085209510.1002/pro.48820799347
     [Google Scholar]
  31. RheeS.G. ChaeH.Z. KimK. Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling.Free Radic. Biol. Med.200538121543155210.1016/j.freeradbiomed.2005.02.02615917183
     [Google Scholar]
  32. WuC.H. FalliniC. TicozziN. KeagleP.J. SappP.C. PiotrowskaK. LoweP. KoppersM. McKenna-YasekD. BaronD.M. KostJ.E. Gonzalez-PerezP. FoxA.D. AdamsJ. TaroniF. TilocaC. LeclercA.L. ChafeS.C. MangrooD. MooreM.J. ZitzewitzJ.A. XuZ.S. van den BergL.H. GlassJ.D. SicilianoG. CirulliE.T. GoldsteinD.B. SalachasF. MeiningerV. RossollW. RattiA. GelleraC. BoscoD.A. BassellG.J. SilaniV. DroryV.E. BrownR.H.Jr LandersJ.E. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis.Nature2012488741249950310.1038/nature1128022801503
     [Google Scholar]
  33. TeyssouE. ChartierL. RousselD. PereraN.D. NemazanyyI. LanguiD. AlbertM. LarmonierT. SakerS. SalachasF. PradatP.F. MeiningerV. RavassardP. CôtéF. LobsigerC.S. BoilléeS. TurnerB.J. SeilheanD. MillecampsS. The amyotrophic lateral sclerosis m114t pfn1 mutation deregulates alternative autophagy pathways and mitochondrial homeostasis.Int. J. Mol. Sci.20222310569410.3390/ijms2310569435628504
     [Google Scholar]
/content/journals/ppl/10.2174/0109298665374669250627205138
Loading
Serum and Urinary Proteomic Signatures Revealing Redox and Metabolic Dysregulation in Acute Achilles Tendon Rupture
PPL 32, 437 (2025); https://doi.org/10.2174/0109298665374669250627205138
/content/journals/ppl/10.2174/0109298665374669250627205138
/content/journals/ppl/10.2174/0109298665374669250627205138
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Achilles tendon rupture; biomarkers; ITRAQ; label-free proteomics; proteome profile; system biology

Most Cited Most Cited RSS feed

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