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PloS one2015; 10(4); e0122220; doi: 10.1371/journal.pone.0122220

Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.

Abstract: It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral) tendons were regionally sampled (medial and lateral halves each divided into six 3 cm regions) for histologic (scoring and immunohistochemistry) and gene expression (real time PCR) analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03) with no differences between overstressed (medial) and stress-deprived (lateral) tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02), with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02) and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001). Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001), whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001). In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes and re-injury in clinical cases. Our data suggest that successful treatments of focal injuries will need to address pathology in the entire tendon, and that better methods to monitor the development and resolution of tendinopathy are required.
Publication Date: 2015-04-02 PubMed ID: 25837713PubMed Central: PMC4383631DOI: 10.1371/journal.pone.0122220Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the widespread histological and gene expression changes in flexor tendons of horses following a surgical injury. The study suggests that localized injuries of this nature significantly affect the entire tendon, leading to a rapid development of tendinopathy and potentially contributing to poor treatment outcomes and a higher likelihood of re-injury.

Methodology

  • The experimental setup involved a surgical half-transection of a single forelimb tendon in six horses, while a similar surgery, known as a sham operation, was carried out on one tendon in three other horses. The sham operation serves as a control measure, providing a comparison point for the surgical injury.
  • At six weeks post-surgery, the horses were euthanized and their injured tendons (the ones transected or sham-operated) were sampled for histological and gene expression analyses. This also included the non-operated contralateral tendons to be compared as control.

Findings: Histological Changes

  • The histopathology score, an indicator of tissue changes following an injury, was significantly higher in transected tendons as compared to the control tendons. This was true across all regions of the tendon, except the most distal ones.
  • Proteoglycan scores, indicative of proteins that heavily populate connective tissues like tendons, also showed an increase following transection in all but the most proximal regions of the tendons.

Findings: Gene Expression Changes

  • Post-surgery, the gene expression for components of the extracellular matrix (part of the tendon’s microenvironment), namely aggrecan, versican, biglycan, lumican, collagen types I, II, and III, Matrix metallopeptidase 14 (MMP14) and tissue inhibitor of metalloproteinase 1(TIMP1) increased significantly in transected tendons compared to control tendons.
  • The gene expression for a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4), Matrix metallopeptidase 3 (MMP3) and tissue inhibitor of metalloproteinase 3(TIMP3) decreased significantly following tendon transection.

Correlations & Implications

  • The research identified positive correlations between certain gene expressions and all histopathology scores. For instance, expressions of aggrecan, biglycan, fibromodulin, and collagen types I and III correlated positively with histopathology scores.
  • The findings imply that surgical injuries of tendons create widespread changes, not confined to the injury site. These changes may contribute to poor functional outcomes and an increased risk of re-injury, highlighting the need for therapeutic approaches addressing the entire tendon instead of a localized treatment. Furthermore, it underscores the necessity for better methods to monitor tendinopathy development and resolution.

Cite This Article

APA
Jacobson E, Dart AJ, Mondori T, Horadogoda N, Jeffcott LB, Little CB, Smith MM. (2015). Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons. PLoS One, 10(4), e0122220. https://doi.org/10.1371/journal.pone.0122220

Publication

ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 10
Issue: 4
Pages: e0122220
PII: e0122220

Researcher Affiliations

Jacobson, Else
    Dart, Andrew J
    • Research and Clinical Training Unit, University Veterinary Teaching Hospital, University of Sydney, Camden, New South Wales, Australia.
    Mondori, Takamitsu
    • Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research, Kolling Institute of Medical Research (University of Sydney) at Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
    Horadogoda, Neil
    • Research and Clinical Training Unit, University Veterinary Teaching Hospital, University of Sydney, Camden, New South Wales, Australia.
    Jeffcott, Leo B
    • Research and Clinical Training Unit, University Veterinary Teaching Hospital, University of Sydney, Camden, New South Wales, Australia.
    Little, Christopher B
    • Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research, Kolling Institute of Medical Research (University of Sydney) at Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
    Smith, Margaret M
    • Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research, Kolling Institute of Medical Research (University of Sydney) at Royal North Shore Hospital, St. Leonards, New South Wales, Australia.

    MeSH Terms

    • Animals
    • Extracellular Matrix Proteins / genetics
    • Extracellular Matrix Proteins / metabolism
    • Gene Expression
    • Horse Diseases / genetics
    • Horse Diseases / metabolism
    • Horse Diseases / pathology
    • Horses / genetics
    • Horses / injuries
    • Horses / metabolism
    • Immunohistochemistry
    • Male
    • Models, Biological
    • Proteoglycans / genetics
    • Proteoglycans / metabolism
    • Tendinopathy / genetics
    • Tendinopathy / metabolism
    • Tendinopathy / veterinary
    • Tendon Injuries / genetics
    • Tendon Injuries / metabolism
    • Tendon Injuries / veterinary
    • Tendons / metabolism
    • Tendons / pathology

    Conflict of Interest Statement

    The authors have declared that no competing interests exist.

    References

    This article includes 71 references
    1. Abate M, Silbernagel KG, Siljeholm C, Di Iorio A, De Amicis D, Salini V, Werner S, Paganelli R. Pathogenesis of tendinopathies: inflammation or degeneration?. Arthritis Res Ther 2009;11(3):235.
      doi: 10.1186/ar2723pmc: PMC2714139pubmed: 19591655google scholar: lookup
    2. Dowling BA, Dart AJ, Hodgson DR, Smith RK. Superficial digital flexor tendonitis in the horse.. Equine Vet J 2000 Sep;32(5):369-78.
      pubmed: 11037257doi: 10.2746/042516400777591138google scholar: lookup
    3. Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling.. J Musculoskelet Neuronal Interact 2006 Apr-Jun;6(2):181-90.
      pubmed: 16849830
    4. Sobhani S, Dekker R, Postema K, Dijkstra PU. Epidemiology of ankle and foot overuse injuries in sports: A systematic review.. Scand J Med Sci Sports 2013 Dec;23(6):669-86.
    5. Slager RF. From Little League to big league, the weak spot is the arm.. Am J Sports Med 1977 Mar-Apr;5(2):37-48.
      pubmed: 848635doi: 10.1177/036354657700500201google scholar: lookup
    6. Dy CJ, Daluiski A, Do HT, Hernandez-Soria A, Marx R, Lyman S. The epidemiology of reoperation after flexor tendon repair.. J Hand Surg Am 2012 May;37(5):919-24.
      pubmed: 22459656doi: 10.1016/j.jhsa.2012.02.003google scholar: lookup
    7. Donaldson PR. Surgical versus nonsurgical treatment of acute Achilles tendon rupture.. Clin J Sport Med 2012 Mar;22(2):169-70.
      doi: 10.1097/JSM.0b013e31824c2b2cpubmed: 22388346google scholar: lookup
    8. Nilsson-Helander K, Silbernagel KG, Thomeé R, Faxén E, Olsson N, Eriksson BI, Karlsson J. Acute achilles tendon rupture: a randomized, controlled study comparing surgical and nonsurgical treatments using validated outcome measures.. Am J Sports Med 2010 Nov;38(11):2186-93.
      doi: 10.1177/0363546510376052pubmed: 20802094google scholar: lookup
    9. Wilkins R, Bisson LJ. Operative versus nonoperative management of acute Achilles tendon ruptures: a quantitative systematic review of randomized controlled trials.. Am J Sports Med 2012 Sep;40(9):2154-60.
      doi: 10.1177/0363546512453293pubmed: 22802271google scholar: lookup
    10. Hägglund M, Waldén M, Ekstrand J. Previous injury as a risk factor for injury in elite football: a prospective study over two consecutive seasons.. Br J Sports Med 2006 Sep;40(9):767-72.
      pmc: PMC2564391pubmed: 16855067doi: 10.1136/bjsm.2006.026609google scholar: lookup
    11. Petersen J, Thorborg K, Nielsen MB, Hölmich P. Acute hamstring injuries in Danish elite football: a 12-month prospective registration study among 374 players.. Scand J Med Sci Sports 2010 Aug;20(4):588-92.
    12. Bey MJ, Derwin KA. Measurement of in vivo tendon function.. J Shoulder Elbow Surg 2012 Feb;21(2):149-57.
      doi: 10.1016/j.jse.2011.10.023pubmed: 22244057google scholar: lookup
    13. Voleti PB, Buckley MR, Soslowsky LJ. Tendon healing: repair and regeneration.. Annu Rev Biomed Eng 2012;14:47-71.
    14. Smith MM, Sakurai G, Smith SM, Young AA, Melrose J, Stewart CM, Appleyard RC, Peterson JL, Gillies RM, Dart AJ, Sonnabend DH, Little CB. Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain.. Arthritis Rheum 2008 Apr;58(4):1055-66.
      doi: 10.1002/art.23388pubmed: 18383380google scholar: lookup
    15. Kannus P, Józsa L. Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients.. J Bone Joint Surg Am 1991 Dec;73(10):1507-25.
      pubmed: 1748700
    16. Tallon C, Maffulli N, Ewen SW. Ruptured Achilles tendons are significantly more degenerated than tendinopathic tendons.. Med Sci Sports Exerc 2001 Dec;33(12):1983-90.
    17. Avella CS, Ely ER, Verheyen KL, Price JS, Wood JL, Smith RK. Ultrasonographic assessment of the superficial digital flexor tendons of National Hunt racehorses in training over two racing seasons.. Equine Vet J 2009 May;41(5):449-54.
      pubmed: 19642404doi: 10.2746/042516409x391042google scholar: lookup
    18. Williams RB, Harkins LS, Hammond CJ, Wood JL. Racehorse injuries, clinical problems and fatalities recorded on British racecourses from flat racing and National Hunt racing during 1996, 1997 and 1998.. Equine Vet J 2001 Sep;33(5):478-86.
      pubmed: 11558743doi: 10.2746/042516401776254808google scholar: lookup
    19. Reardon RJ, Boden LA, Mellor DJ, Love S, Newton JR, Stirk AJ, Parkin TD. Risk factors for superficial digital flexor tendinopathy in Thoroughbred racehorses in steeplechase starts in the United Kingdom (2001-2009).. Vet J 2013 Mar;195(3):325-30.
      doi: 10.1016/j.tvjl.2012.06.033pubmed: 22840205google scholar: lookup
    20. O'Meara B, Bladon B, Parkin TD, Fraser B, Lischer CJ. An investigation of the relationship between race performance and superficial digital flexor tendonitis in the Thoroughbred racehorse.. Equine Vet J 2010 May;42(4):322-6.
    21. Oikawa M, Kasashima Y. The Japanese experience with tendonitis in racehorses. J Equine Sci 13: 41–56.
    22. Dyson SJ. Medical management of superficial digital flexor tendonitis: a comparative study in 219 horses (1992-2000).. Equine Vet J 2004 Jul;36(5):415-9.
      pubmed: 15253082doi: 10.2746/0425164044868422google scholar: lookup
    23. Crevier-Denoix N, Collobert C, Pourcelot P, Denoix JM, Sanaa M, Geiger D, Bernard N, Ribot X, Bortolussi C, Bousseau B. Mechanical properties of pathological equine superficial digital flexor tendons.. Equine Vet J Suppl 1997 May;(23):23-6.
    24. Dakin SG, Dudhia J, Smith RK. Resolving an inflammatory concept: the importance of inflammation and resolution in tendinopathy.. Vet Immunol Immunopathol 2014 Apr 15;158(3-4):121-7.
    25. Riley GP. Gene expression and matrix turnover in overused and damaged tendons.. Scand J Med Sci Sports 2005 Aug;15(4):241-51.
    26. de Mos M, van El B, DeGroot J, Jahr H, van Schie HT, van Arkel ER, Tol H, Heijboer R, van Osch GJ, Verhaar JA. Achilles tendinosis: changes in biochemical composition and collagen turnover rate.. Am J Sports Med 2007 Sep;35(9):1549-56.
      pubmed: 17478653doi: 10.1177/0363546507301885google scholar: lookup
    27. Patterson-Kane JC, Firth EC. The pathobiology of exercise-induced superficial digital flexor tendon injury in Thoroughbred racehorses.. Vet J 2009 Aug;181(2):79-89.
      doi: 10.1016/j.tvjl.2008.02.009pubmed: 18406184google scholar: lookup
    28. Sztrolovics R, White RJ, Roughley PJ, Mort JS. The mechanism of aggrecan release from cartilage differs with tissue origin and the agent used to stimulate catabolism.. Biochem J 2002 Mar 1;362(Pt 2):465-72.
      pmc: PMC1222408pubmed: 11853556doi: 10.1042/0264-6021:3620465google scholar: lookup
    29. Bustin SA, Nolan T. Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction.. J Biomol Tech 2004 Sep;15(3):155-66.
      pmc: PMC2291693pubmed: 15331581
    30. Corps AN, Robinson AH, Movin T, Costa ML, Hazleman BL, Riley GP. Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy.. Rheumatology (Oxford) 2006 Mar;45(3):291-4.
      pubmed: 16219640doi: 10.1093/rheumatology/kei152google scholar: lookup
    31. Warden SJ. Animal models for the study of tendinopathy.. Br J Sports Med 2007 Apr;41(4):232-40.
      pmc: PMC2658951pubmed: 17127722doi: 10.1136/bjsm.2006.032342google scholar: lookup
    32. Lake SP, Ansorge HL, Soslowsky LJ. Animal models of tendinopathy.. Disabil Rehabil 2008;30(20-22):1530-41.
      pubmed: 18608372doi: 10.1080/09638280701785460google scholar: lookup
    33. Lui PP, Maffulli N, Rolf C, Smith RK. What are the validated animal models for tendinopathy?. Scand J Med Sci Sports 2011 Feb;21(1):3-17.
    34. Longo UG, Forriol F, Campi S, Maffulli N, Denaro V. Animal models for translational research on shoulder pathologies: from bench to bedside.. Sports Med Arthrosc Rev 2011 Sep;19(3):184-93.
      doi: 10.1097/JSA.0b013e318205470epubmed: 21822100google scholar: lookup
    35. Archambault JM, Jelinsky SA, Lake SP, Hill AA, Glaser DL, Soslowsky LJ. Rat supraspinatus tendon expresses cartilage markers with overuse.. J Orthop Res 2007 May;25(5):617-24.
      pubmed: 17318892doi: 10.1002/jor.20347google scholar: lookup
    36. Watts AE, Nixon AJ, Yeager AE, Mohammed HO. A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis.. Equine Vet J 2012 Sep;44(5):576-86.
    37. Schramme M, Hunter S, Campbell N, Blikslager A, Smith R. A surgical tendonitis model in horses: technique, clinical, ultrasonographic and histological characterisation.. Vet Comp Orthop Traumatol 2010;23(4):231-9.
      doi: 10.3415/VCOT-09-10-0106pubmed: 20585715google scholar: lookup
    38. Watkins JP, Auer JA, Gay S, Morgan SJ. Healing of surgically created defects in the equine superficial digital flexor tendon: collagen-type transformation and tissue morphologic reorganization.. Am J Vet Res 1985 Oct;46(10):2091-6.
      pubmed: 4062012
    39. Crevier-Denoix N, Ruel Y, Dardillat C, Jerbi H, Sanaa M, Collobert-Laugier C, Ribot X, Denoix JM, Pourcelot P. Correlations between mean echogenicity and material properties of normal and diseased equine superficial digital flexor tendons: an in vitro segmental approach.. J Biomech 2005 Nov;38(11):2212-20.
    40. Peffers MJ, Thorpe CT, Collins JA, Eong R, Wei TK, Screen HR, Clegg PD. Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation.. J Biol Chem 2014 Sep 12;289(37):25867-78.
      doi: 10.1074/jbc.M114.566554pmc: PMC4162187pubmed: 25077967google scholar: lookup
    41. Rand T, Bindeus T, Alton K, Voegele T, Kukla C, Stanek C, Imhof H. Low-field magnetic resonance imaging (0.2 T) of tendons with sonographic and histologic correlation. Cadaveric study.. Invest Radiol 1998 Aug;33(8):433-8.
    42. Docking SI, Daffy J, van Schie HT, Cook JL. Tendon structure changes after maximal exercise in the Thoroughbred horse: use of ultrasound tissue characterisation to detect in vivo tendon response.. Vet J 2012 Dec;194(3):338-42.
      doi: 10.1016/j.tvjl.2012.04.024pubmed: 22658820google scholar: lookup
    43. van Hamel SE, Bergman HJ, Puchalski SM, de Groot MW, van Weeren PR. Contrast-enhanced computed tomographic evaluation of the deep digital flexor tendon in the equine foot compared to macroscopic and histological findings in 23 limbs.. Equine Vet J 2014 May;46(3):300-5.
      doi: 10.1111/evj.12129pubmed: 23808755google scholar: lookup
    44. Demehri S, Chalian M, Farahani SJ, Fishman EK, Fayad LM. Detection and characterization of tendon abnormalities with multidetector computed tomography.. J Comput Assist Tomogr 2014 Mar-Apr;38(2):299-307.
      doi: 10.1097/RCT.0b013e3182aa72bfpubmed: 24625602google scholar: lookup
    45. Sivaguru M, Eichorst JP, Durgam S, Fried GA, Stewart AA, Stewart MC. Imaging horse tendons using multimodal 2-photon microscopy.. Methods 2014 Mar 15;66(2):256-67.
      doi: 10.1016/j.ymeth.2013.07.016pubmed: 23871762google scholar: lookup
    46. Dyment NA, Kazemi N, Aschbacher-Smith LE, Barthelery NJ, Kenter K, Gooch C, Shearn JT, Wylie C, Butler DL. The relationships among spatiotemporal collagen gene expression, histology, and biomechanics following full-length injury in the murine patellar tendon.. J Orthop Res 2012 Jan;30(1):28-36.
      doi: 10.1002/jor.21484pmc: PMC3181390pubmed: 21698662google scholar: lookup
    47. Lui PP, Cheuk YC, Lee YW, Chan KM. Ectopic chondro-ossification and erroneous extracellular matrix deposition in a tendon window injury model.. J Orthop Res 2012 Jan;30(1):37-46.
      doi: 10.1002/jor.21495pubmed: 21761446google scholar: lookup
    48. Jelinsky SA, Rodeo SA, Li J, Gulotta LV, Archambault JM, Seeherman HJ. Regulation of gene expression in human tendinopathy.. BMC Musculoskelet Disord 2011 May 3;12:86.
      doi: 10.1186/1471-2474-12-86pmc: PMC3095578pubmed: 21539748google scholar: lookup
    49. Karousou E, Ronga M, Vigetti D, Passi A, Maffulli N. Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture.. Clin Orthop Relat Res 2008 Jul;466(7):1577-82.
      pmc: PMC2505242pubmed: 18425559doi: 10.1007/s11999-008-0255-ygoogle scholar: lookup
    50. Samiric T, Parkinson J, Ilic MZ, Cook J, Feller JA, Handley CJ. Changes in the composition of the extracellular matrix in patellar tendinopathy.. Matrix Biol 2009 May;28(4):230-6.
      doi: 10.1016/j.matbio.2009.04.001pubmed: 19371780google scholar: lookup
    51. Corps AN, Robinson AH, Harrall RL, Avery NC, Curry VA, Hazleman BL, Riley GP. Changes in matrix protein biochemistry and the expression of mRNA encoding matrix proteins and metalloproteinases in posterior tibialis tendinopathy.. Ann Rheum Dis 2012 May;71(5):746-52.
    52. Jones GC, Corps AN, Pennington CJ, Clark IM, Edwards DR, Bradley MM, Hazleman BL, Riley GP. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon.. Arthritis Rheum 2006 Mar;54(3):832-42.
      pubmed: 16508964doi: 10.1002/art.21672google scholar: lookup
    53. Ireland D, Harrall R, Curry V, Holloway G, Hackney R, Hazleman B, Riley G. Multiple changes in gene expression in chronic human Achilles tendinopathy.. Matrix Biol 2001 Jun;20(3):159-69.
      pubmed: 11420148doi: 10.1016/s0945-053x(01)00128-7google scholar: lookup
    54. Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB. Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons.. Am J Sports Med 2004 Jul-Aug;32(5):1223-9.
      pubmed: 15262646doi: 10.1177/0363546503262200google scholar: lookup
    55. Lundin AC, Aspenberg P, Eliasson P. Trigger finger, tendinosis, and intratendinous gene expression.. Scand J Med Sci Sports 2014 Apr;24(2):363-8.
    56. Leigh DR, Abreu EL, Derwin KA. Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture.. J Orthop Res 2008 Oct;26(10):1306-12.
      doi: 10.1002/jor.20650pmc: PMC6100787pubmed: 18404723google scholar: lookup
    57. Thornton GM, Hart DA. The interface of mechanical loading and biological variables as they pertain to the development of tendinosis.. J Musculoskelet Neuronal Interact 2011 Jun;11(2):94-105.
      pubmed: 21625046
    58. Hosaka YZ, Takahashi H, Uratsuji T, Tangkawattana P, Ueda H, Takehana K. Comparative study of the characteristics and properties of tendinocytes derived from three tendons in the equine forelimb.. Tissue Cell 2010 Feb;42(1):9-17.
      doi: 10.1016/j.tice.2009.06.002pubmed: 19640554google scholar: lookup
    59. John T, Lodka D, Kohl B, Ertel W, Jammrath J, Conrad C, Stoll C, Busch C, Schulze-Tanzil G. Effect of pro-inflammatory and immunoregulatory cytokines on human tenocytes.. J Orthop Res 2010 Aug;28(8):1071-7.
      doi: 10.1002/jor.21079pubmed: 20127972google scholar: lookup
    60. Scott A, Lian Ø, Roberts CR, Cook JL, Handley CJ, Bahr R, Samiric T, Ilic MZ, Parkinson J, Hart DA, Duronio V, Khan KM. Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee.. Scand J Med Sci Sports 2008 Aug;18(4):427-35.
    61. Parkinson J, Samiric T, Ilic MZ, Cook J, Feller JA, Handley CJ. Change in proteoglycan metabolism is a characteristic of human patellar tendinopathy.. Arthritis Rheum 2010 Oct;62(10):3028-35.
      doi: 10.1002/art.27587pubmed: 20533294google scholar: lookup
    62. Attia M, Scott A, Carpentier G, Lian O, Van Kuppevelt T, Gossard C, Papy-Garcia D, Tassoni MC, Martelly I. Greater glycosaminoglycan content in human patellar tendon biopsies is associated with more pain and a lower VISA score.. Br J Sports Med 2014 Mar;48(6):469-75.
      doi: 10.1136/bjsports-2013-092633pubmed: 24100290google scholar: lookup
    63. Mazzocca AD, McCarthy MB, Ledgard FA, Chowaniec DM, McKinnon WJ Jr, Delaronde S, Rubino LJ, Apolostakos J, Romeo AA, Arciero RA, Beitzel K. Histomorphologic changes of the long head of the biceps tendon in common shoulder pathologies.. Arthroscopy 2013 Jun;29(6):972-81.
      doi: 10.1016/j.arthro.2013.02.002pubmed: 23571131google scholar: lookup
    64. Riley GP, Harrall RL, Constant CR, Chard MD, Cawston TE, Hazleman BL. Glycosaminoglycans of human rotator cuff tendons: changes with age and in chronic rotator cuff tendinitis.. Ann Rheum Dis 1994 Jun;53(6):367-76.
      pmc: PMC1005351pubmed: 8037495doi: 10.1136/ard.53.6.367google scholar: lookup
    65. Burssens A, Forsyth R, Bongaerts W, Jagodzinski M, Mahieu N, Praet M, Victor J. Arguments for an increasing differentiation towards fibrocartilaginous components in midportion Achilles tendinopathy.. Knee Surg Sports Traumatol Arthrosc 2013 Jun;21(6):1459-67.
      doi: 10.1007/s00167-012-2203-3pubmed: 23001016google scholar: lookup
    66. Corps AN, Robinson AH, Movin T, Costa ML, Ireland DC, Hazleman BL, Riley GP. Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies.. Rheumatology (Oxford) 2004 Aug;43(8):969-72.
      pubmed: 15138331doi: 10.1093/rheumatology/keh222google scholar: lookup
    67. Watanabe T, Imamura Y, Suzuki D, Hosaka Y, Ueda H, Hiramatsu K, Takehana K. Concerted and adaptive alignment of decorin dermatan sulfate filaments in the graded organization of collagen fibrils in the equine superficial digital flexor tendon.. J Anat 2012 Feb;220(2):156-63.
    68. Alfredson H, Lorentzon M, Bäckman S, Bäckman A, Lerner UH. cDNA-arrays and real-time quantitative PCR techniques in the investigation of chronic Achilles tendinosis.. J Orthop Res 2003 Nov;21(6):970-5.
      pubmed: 14554207doi: 10.1016/s0736-0266(03)00107-4google scholar: lookup
    69. Stanton H, Melrose J, Little CB, Fosang AJ. Proteoglycan degradation by the ADAMTS family of proteinases.. Biochim Biophys Acta 2011 Dec;1812(12):1616-29.
      pubmed: 21914474doi: 10.1016/j.bbadis.2011.08.009google scholar: lookup
    70. Corps AN, Jones GC, Harrall RL, Curry VA, Hazleman BL, Riley GP. The regulation of aggrecanase ADAMTS-4 expression in human Achilles tendon and tendon-derived cells.. Matrix Biol 2008 Jun;27(5):393-401.
    71. Zhang G, Ezura Y, Chervoneva I, Robinson PS, Beason DP, Carine ET, Soslowsky LJ, Iozzo RV, Birk DE. Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development.. J Cell Biochem 2006 Aug 15;98(6):1436-49.
      pubmed: 16518859doi: 10.1002/jcb.20776google scholar: lookup

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      doi: 10.3390/ijms222312798pubmed: 34884602google scholar: lookup
    2. Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS, Mauck RL, King WJ, Engiles JB, Ortved KF. Evaluation of Autologous Protein Solution Injection for Treatment of Superficial Digital Flexor Tendonitis in an Equine Model.. Front Vet Sci 2021;8:697551.
      doi: 10.3389/fvets.2021.697551pubmed: 34291103google scholar: lookup
    3. Oreff GL, Fenu M, Vogl C, Ribitsch I, Jenner F. Species variations in tenocytes' response to inflammation require careful selection of animal models for tendon research.. Sci Rep 2021 Jun 14;11(1):12451.
      doi: 10.1038/s41598-021-91914-9pubmed: 34127759google scholar: lookup
    4. Sánchez-Sánchez JL, Calderón-Díez L, Herrero-Turrión J, Méndez-Sánchez R, Arias-Buría JL, Fernández-de-Las-Peñas C. Changes in Gene Expression Associated with Collagen Regeneration and Remodeling of Extracellular Matrix after Percutaneous Electrolysis on Collagenase-Induced Achilles Tendinopathy in an Experimental Animal Model: A Pilot Study.. J Clin Med 2020 Oct 15;9(10).
      doi: 10.3390/jcm9103316pubmed: 33076550google scholar: lookup
    5. Pechanec MY, Boyd TN, Baar K, Mienaltowski MJ. Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro.. BMC Musculoskelet Disord 2020 Sep 23;21(1):627.
      doi: 10.1186/s12891-020-03650-2pubmed: 32967653google scholar: lookup
    6. Easley J, Johnson J, Regan D, Hackett E, Romeo AA, Schlegel T, Broomfield C, Puttlitz C, McGilvray K. Partial Infraspinatus Tendon Transection as a Means for the Development of a Translational Ovine Chronic Rotator Cuff Disease Model.. Vet Comp Orthop Traumatol 2020 May;33(3):212-219.
      doi: 10.1055/s-0040-1701650pubmed: 32232814google scholar: lookup
    7. Tsang AS, Dart AJ, Biasutti SA, Jeffcott LB, Smith MM, Little CB. Effects of tendon injury on uninjured regional tendons in the distal limb: An in-vivo study using an ovine tendinopathy model.. PLoS One 2019;14(4):e0215830.
      doi: 10.1371/journal.pone.0215830pubmed: 31013317google scholar: lookup
    8. Biasutti S, Dart A, Smith M, Blaker C, Clarke E, Jeffcott L, Little C. Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy.. PLoS One 2017;12(10):e0185282.
      doi: 10.1371/journal.pone.0185282pubmed: 29023489google scholar: lookup
    9. Jacobson E, Dart AJ, Mondori T, Horadogoda N, Jeffcott LB, Little CB, Smith MM. Correction: Focal Experimental Injury Leads to Widespread Gene Expression and Histologic Changes in Equine Flexor Tendons.. PLoS One 2016;11(3):e0150823.
      doi: 10.1371/journal.pone.0150823pubmed: 26930413google scholar: lookup