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image of Serum and Urinary Proteomic Signatures Revealing Redox and Metabolic Dysregulation in Acute Achilles Tendon Rupture

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.

Method

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.

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/content/journals/ppl/10.2174/0109298665374669250627205138
2025-07-09
2025-09-13
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References

  1. Jielile J. Badalihan A. Qianman B. Satewalede T. Wuerliebieke J. Kelamu M. Jialihasi A. 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. 2016 24 7 2148 2155 10.1007/s00167‑015‑3598‑4 25894749
    [Google Scholar]
  2. Jielile J. Sabirhazi G. Hu G. Chen J. Aldyarhan K. Zheyiken J. Zhao Q. Bai J. Novel surgical technique and early kinesiotherapy for acute Achilles tendon rupture. Foot Ankle Int. 2012 33 12 1119 1127 10.3113/FAI.2012.1119 23199864
    [Google Scholar]
  3. Mansfield K. Dopke K. Koroneos Z. Bonaddio V. Adeyemo A. Aynardi M. Achilles tendon ruptures and repair in athletes—a review of sports-related achilles injuries and return to play. Curr. Rev. Musculoskelet. Med. 2022 15 5 353 361 10.1007/s12178‑022‑09774‑3 35804260
    [Google Scholar]
  4. Aisaiding A. Wang J. Maimaiti R. Jialihasi A. Aibek R. Qianman B. Shawutali N. Badelihan A. Bahetiya W. Kubai A. Kelamu M. Nuerdoula Y. Makemutibieke E. Bakyt Y. Wuerliebieke J. Jielile J. A novel minimally invasive surgery combined with early exercise therapy promoting tendon regeneration in the treatment of spontaneous Achilles tendon rupture. Injury 2018 49 3 712 719 10.1016/j.injury.2017.10.046 29153451
    [Google Scholar]
  5. Badalihan A. Aihemaiti A. Shawutali N. Jielile J. Jialihasi A. Tangkejie W. Nuerdoula Y. Satewalede T. Hunapiya B. Niyazebieke H. Hezibieke H. Zhao Q. Bahetijiang A. Kelamu M. Qianman B. 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. 2015 54 2 153 159 10.1053/j.jfas.2014.12.002 25703445
    [Google Scholar]
  6. Sode J. Obel N. Hallas J. Lassen A. Use of fluroquinolone and risk of Achilles tendon rupture: A population-based cohort study. Eur. J. Clin. Pharmacol. 2007 63 5 499 503 10.1007/s00228‑007‑0265‑9 17334751
    [Google Scholar]
  7. van der Linden P.D. Sturkenboom M.C.J.M. Herings R.M.C. Leufkens H.M.G. Rowlands S. Stricker B.H.C. Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. Arch. Intern. Med. 2003 163 15 1801 1807 10.1001/archinte.163.15.1801 12912715
    [Google Scholar]
  8. Jiasharete J.J. Qianman B. Shawutali N. Tuomilisi J. Badelihan A. Jialihasi A. Achilles Tendon Surgery. Tianjin, China Science and Technology Press 2019 932 1050
    [Google Scholar]
  9. Horvath D. Horvath M. A case of nontraumatic simultaneous bilateral Achilles tendon rupture. J. Am. Assoc. Nurse Pract. 2023 35 12 853 855 10.1097/JXX.0000000000000906 37335847
    [Google Scholar]
  10. Holmes G.B. Lin J. Etiologic factors associated with symptomatic achilles tendinopathy. Foot Ankle Int. 2006 27 11 952 959 10.1177/107110070602701115 17144959
    [Google Scholar]
  11. Kannus P. Józsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J. Bone Joint Surg. Am. 1991 73 10 1507 1525 10.2106/00004623‑199173100‑00009 1748700
    [Google Scholar]
  12. Arner O. Lindholm A. Orell S.R. Histologic changes in subcutaneous rupture of the Achilles tendon; a study of 74 cases. Acta Chir. Scand. 1959 116 5-6 484 490 13660717
    [Google Scholar]
  13. Józsa L. Kannus P. Histopathological findings in spontaneous tendon ruptures. Scand. J. Med. Sci. Sports 1997 7 2 113 118 10.1111/j.1600‑0838.1997.tb00127.x 9211612
    [Google Scholar]
  14. Jielile J. Asilehan B. Wupuer A. Qianman B. Jialihasi A. Tangkejie W. Maimaitiaili A. Shawutali N. Badelhan A. Niyazebieke H. Aizezi A. Aisaiding A. Bakyt Y. Aibek R. Wuerliebieke J. Early ankle mobilization promotes healing in a rabbit model of achilles tendon rupture. Orthopedics 2016 39 1 e117 e126 10.3928/01477447‑20160106‑01 26821224
    [Google Scholar]
  15. Rozanova S. Barkovits K. Nikolov M. Schmidt C. Urlaub H. Marcus K. Quantitative mass spectrometry-based proteomics: An overview. Methods Mol. Biol. 2021 2228 85 116 10.1007/978‑1‑0716‑1024‑4_8 33950486
    [Google Scholar]
  16. Hanash S. Disease proteomics. Nature 2003 422 6928 226 232 10.1038/nature01514 12634796
    [Google Scholar]
  17. Mering C. Huynen M. Jaeggi D. Schmidt S. Bork P. Snel B. STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 2003 31 1 258 261 10.1093/nar/gkg034 12519996
    [Google Scholar]
  18. Zhang G. Ezura Y. Chervoneva I. Robinson P.S. Beason D.P. Carine E.T. Soslowsky L.J. Iozzo R.V. Birk D.E. Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development. J. Cell. Biochem. 2006 98 6 1436 1449 10.1002/jcb.20776 16518859
    [Google Scholar]
  19. Raspanti M. Congiu T. Guizzardi S. Structural aspects of the extracellular matrix of the tendon: An atomic force and scanning electron microscopy study. Arch. Histol. Cytol. 2002 65 1 37 43 10.1679/aohc.65.37 12002609
    [Google Scholar]
  20. Caon I. Parnigoni A. Karousou E. Biochemistry of hyaluronan synthesis. Hyaluronan: Structure, Biology and Biotechnology Cham Springer 2023
    [Google Scholar]
  21. (a) Gustav A. Influences of paratendinous innervation and non-neuronal substance P in tendinopathy: Studies on human tendon tissue and an experimental model of Achilles tendinopathy. 2010 Available 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. Lee B.E.J. Luo L. Grandfield K. Andrei C.M. Schwarcz H.P. Identification of collagen fibrils in cross sections of bone by electron energy loss spectroscopy (EELS). Micron 2019 124 102706 10.1016/j.micron.2019.102706 31255883
    [Google Scholar]
  23. Dakin S.G. Martinez F.O. Yapp C. Wells G. Oppermann U. Dean B.J.F. Smith R.D.J. Wheway K. Watkins B. Roche L. Carr A.J. Inflammation activation and resolution in human tendon disease. Sci. Transl. Med. 2015 7 311 311ra173 10.1126/scitranslmed.aac4269 26511510
    [Google Scholar]
  24. Sies H. Oxidative eustress: On constant alert for redox homeostasis. Redox Biol. 2021 41 101867 10.1016/j.redox.2021.101867 33657525
    [Google Scholar]
  25. Gupta V. Bamezai R.N.K. Human pyruvate kinase M2: A multifunctional protein. Protein Sci. 2010 19 11 2031 2044 10.1002/pro.505 20857498
    [Google Scholar]
  26. Blake C.C. Rice D.W. Phosphoglycerate kinase. Philos. Trans. R. Soc. Lond. B Biol. Sci. 1981 293 1063 93 104 10.1098/rstb.1981.0063 6115427
    [Google Scholar]
  27. Fujii H. Miwa S. Other erythrocyte enzyme deficiencies associated with non-haematological symptoms: Phosphoglycerate kinase and phosphofructokinase deficiency. Best Pract. Res. Clin. Haematol. 2000 13 1 141 148 10.1053/beha.1999.0062 10916683
    [Google Scholar]
  28. Raskind W.H. Wijsman E. Pagon R.A. Cox T.C. Bawden M.J. May B.K. Bird T.D. X-linked sideroblastic anemia and ataxia: Linkage to phosphoglycerate kinase at Xq13. Am. J. Hum. Genet. 1991 48 2 335 341 1671320
    [Google Scholar]
  29. Grace R.F. Zanella A. Neufeld E.J. Morton D.H. Eber S. Yaish H. Glader B. Erythrocyte pyruvate kinase deficiency: 2015 status report. Am. J. Hematol. 2015 90 9 825 830 10.1002/ajh.24088 26087744
    [Google Scholar]
  30. Anselment B. Baerend D. Mey E. Buchner J. Weuster-Botz D. Haslbeck M. Experimental optimization of protein refolding with a genetic algorithm. Protein Sci. 2010 19 11 2085 2095 10.1002/pro.488 20799347
    [Google Scholar]
  31. Rhee S.G. Chae H.Z. Kim K. Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic. Biol. Med. 2005 38 12 1543 1552 10.1016/j.freeradbiomed.2005.02.026 15917183
    [Google Scholar]
  32. Wu C.H. Fallini C. Ticozzi N. Keagle P.J. Sapp P.C. Piotrowska K. Lowe P. Koppers M. McKenna-Yasek D. Baron D.M. Kost J.E. Gonzalez-Perez P. Fox A.D. Adams J. Taroni F. Tiloca C. Leclerc A.L. Chafe S.C. Mangroo D. Moore M.J. Zitzewitz J.A. Xu Z.S. van den Berg L.H. Glass J.D. Siciliano G. Cirulli E.T. Goldstein D.B. Salachas F. Meininger V. Rossoll W. Ratti A. Gellera C. Bosco D.A. Bassell G.J. Silani V. Drory V.E. Brown R.H. Jr Landers J.E. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 2012 488 7412 499 503 10.1038/nature11280 22801503
    [Google Scholar]
  33. Teyssou E. Chartier L. Roussel D. Perera N.D. Nemazanyy I. Langui D. Albert M. Larmonier T. Saker S. Salachas F. Pradat P.F. Meininger V. Ravassard P. Côté F. Lobsiger C.S. Boillée S. Turner B.J. Seilhean D. Millecamps S. The amyotrophic lateral sclerosis m114t pfn1 mutation deregulates alternative autophagy pathways and mitochondrial homeostasis. Int. J. Mol. Sci. 2022 23 10 5694 10.3390/ijms23105694 35628504
    [Google Scholar]
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