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Connective tissue research2012; 54(1); 62-69; doi: 10.3109/03008207.2012.734879

Immunolocalization of collagens (I and III) and cartilage oligomeric matrix protein in the normal and injured equine superficial digital flexor tendon.

Abstract: This is a descriptive study of tendon pathology with different structural appearances of repair tissue correlated to immunolocalization of cartilage oligomeric matrix protein (COMP) and type I and III collagens and expression of COMP mRNA. The material consists of nine tendons from seven horses (5-25 years old; mean age of 10 years) with clinical tendinopathy and three normal tendons from horses (3, 3, and 13 years old) euthanized for non-orthopedic reasons. The injured tendons displayed different repair-tissue appearances with organized and disorganized fibroblastic regions as well as areas of necrosis. The normal tendons presented distinct immunoreactivity for COMP and expression of COMP mRNA and type I collagen in the normal aligned fiber structures, but no immunolabeling of type III collagen. However, immunoreactivity for type III collagen was present in the endotenon surrounding the fiber bundles, where no expression of COMP could be seen. Immunostaining for type I and III collagens was present in all of the pathologic regions indicating repair tissue. Interestingly, the granulation tissues showed immunostaining for COMP and expression of COMP mRNA, indicating a role for COMP in repair and remodeling of the tendon after fiber degeneration and rupture. The present results suggest that not only type III collagen but also COMP is involved in the repair and remodeling processes of the tendon.
Publication Date: 2012-12-03 PubMed ID: 23020676PubMed Central: PMC3545546DOI: 10.3109/03008207.2012.734879Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research looks at the structural changes in the tendons of horses with tendinopathy, a type of tendon injury, by analyzing the location and expression levels of certain proteins and collagens. The findings suggest that cartilage oligomeric matrix protein (COMP) and type I and III collagens play important roles in tendon repair and remodeling processes.

Research Context

  • The focus of this study is on equine superficial digital flexor tendon, which is a common site for tendon injuries in horses. These injuries often lead to tendinopathy – a condition resulting in pain, swelling, and impaired function.
  • The researchers looked into the spatial distribution (immunolocalization) of cartilage oligomeric matrix protein (COMP) and type I and III collagens in the equine tendons.
  • The study utilized tendons from ten horses; seven with clinical tendinopathy and three healthy horses. This provided a comparison between normal and injured tendon tissue.

Findings of the Study

  • The injured tendons showed areas of organized and disorganized fibroblastic activity and even areas of necrosis (cell death).
  • In the normal tendons, COMP and type I collagen were present in healthy fiber structures, but type III collagen was absent. However, type III collagen was found in the endotenon – a sheath surrounding the bundles of tendon muscle fibers.
  • Interestingly, both type I and III collagens were present in all pathological regions of the tendon, suggesting their role in the repair process.
  • Notably, the granulation tissues – new connective tissues that form on the surfaces of wounds during the healing process – showed COMP and COMP mRNA expression. This finding suggests that COMP also has a role in tendon repair and remodeling after an injury.

Implications of the Study

  • The findings provide insight into the possible mechanisms of tendon repair in horses, which may be utilized for developing more effective treatments for tendinopathy.
  • The study suggested that type I and III collagens, as well as COMP, are involved in tendon repair and remodeling after damage. This challenges the earlier perception that only type III collagen is involved in tendon repair.
  • With further research, these findings could eventually be translated to human medicine, as tendinopathies are common injuries in many sports and occupations.

Cite This Article

APA
Södersten F, Hultenby K, Heinegård D, Johnston C, Ekman S. (2012). Immunolocalization of collagens (I and III) and cartilage oligomeric matrix protein in the normal and injured equine superficial digital flexor tendon. Connect Tissue Res, 54(1), 62-69. https://doi.org/10.3109/03008207.2012.734879

Publication

ISSN: 1607-8438
NlmUniqueID: 0365263
Country: England
Language: English
Volume: 54
Issue: 1
Pages: 62-69

Researcher Affiliations

Södersten, Fredrik
  • Division of Pathology, Pharmacology and Toxicology, Department of Biomedicine & Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden. fredrik.sodersten@slu.se
Hultenby, Kjell
    Heinegård, Dick
      Johnston, Christopher
        Ekman, Stina

          MeSH Terms

          • Animals
          • Collagen Type I / analysis
          • Collagen Type I / genetics
          • Collagen Type I / metabolism
          • Collagen Type II / analysis
          • Collagen Type II / genetics
          • Collagen Type II / metabolism
          • Extracellular Matrix Proteins / analysis
          • Extracellular Matrix Proteins / metabolism
          • Gene Expression
          • Glycoproteins / analysis
          • Glycoproteins / metabolism
          • Horse Diseases / metabolism
          • Horse Diseases / pathology
          • Horses
          • Matrilin Proteins
          • RNA, Messenger / metabolism
          • Tendon Injuries / metabolism
          • Tendon Injuries / pathology
          • Tendon Injuries / veterinary
          • Tendons / metabolism

          References

          This article includes 48 references
          1. Williams R.B., Harkins L.S., Hammond C.J., Wood J.L.. 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;33:478–486.
            pubmed: 11558743
          2. Nyyssonen T., Luthje P.. Achilles tendon ruptures in South-East Finland between 1986–1996, with special reference to epidemiology, complications of surgery and hospital costs.. Ann. Chir. Gynaecol. 2000;89:53–57.
            pubmed: 10791646
          3. Thorpe C.T., Clegg P.D., Birch H.L.. A review of tendon injury: Why is the equine superficial digital flexor tendon most at risk?. Equine Vet. J. 2010;42:174–180.
            pubmed: 20156256
          4. Dyson S.J.. Medical management of superficial digital flexor tendonitis: A comparative study in 219 horses (1992–2000.. Equine Vet. J. 2004;36:415–419.
            pubmed: 15253082
          5. Benjamin M., Ralphs J.R.. Tendon and ligaments—An overview.. Histol. Histopathol. 1997;12:1135–1144.
            pubmed: 9302572
          6. Lapiere C.M., Nusgens B., Pierard G.E.. Interaction between collagen type I and type III in conditioning bundles organization.. Connective Tissue Res. 1977;5:21–29.
            pubmed: 141359
          7. Wang J.H.-C.. Mechanobiology of tendon—Review.. J. Biomechanics. 2006;39:1563–1582.
            pubmed: 16000201
          8. Zhang G., Young B.B., Ezura Y., Favata M., Soslowsky L.J., Chakravarti S., Birk D.E.. Development of tendon structure and function: Regulation of collagen fibrillogenesis.. J. Musculoskelet. Neuronal. Interact. 2005;5:5–21.
            pubmed: 15788867
          9. Birk D.E., Mayne R.. Localization of collagen types I, III and V during tendon development. Changes in collagen types I and III are correlated with changes in fibril diameter.. Eur. J. Cell Biol. 1997;72:352–361.
            pubmed: 9127735
          10. Abrahamsson S.O.. Matrix metabolism and healing in the flexor tendon—Review.. Scand. J. Plast. Reconstr. Surg. Handsurg. 1991;23(Suppl.):1–51.
            pubmed: 1947826
          11. Vogel K.G., Sandy J.D., Pogány G., Robbins J.R.. Aggrecan in bovine tendon.. Matrix Biol. 1994;14:171–179.
            pubmed: 7520336
          12. Svensson L., Aszódi A., Reinholt F.P., Fässler R., Heinegård D., Oldberg Å.. Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon.. J. Biol. Chem. 1999;274:9636–9647.
            pubmed: 10092650
          13. Graham H.K., Holmes D.F., Watson R.B., Kadler K.E.. Identification of Collagen fibril fusion during vertebrate tendon morphogenesis. The process relies on unipolar fibrils and is regulated by collagen-proteoglycan interaction.. J. Mol. Biol. 1999;295:891–902.
            pubmed: 10656798
          14. Hedbom E., Antonsson P., Hjerpe A., Aeschlimann D., Paulsson M., Rosa-Pimentel E., Sommarin Y., Wendel M., Oldberg Å., Heinegård D.. Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage.. J. Biol. Chem. 1992;267:6132–6136.
            pubmed: 1556121
          15. Di Cesare P., Hauser N., Lehman D., Pasumarti S., Paulsson M.. Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon.. FEBS Lett. 1994;354:237–240.
            pubmed: 7957930
          16. Mörgelin M., Heinegård D., Engel J., Electron P.M.. Microscopy of native cartilage oligomeric matrix protein purified from the swarm rat chondrosarcoma reveals a five-armed structure.. J. Biol. Chem. 1992;267:6137–6141.
            pubmed: 1556122
          17. Oldberg A., Antonsson P., Lindblom K., Heinegård D.. COMP (cartilage oligomeric matrix protein) is structurally related to the thrombospondins.. J. Biol. Chem. 1992;267:22346–22350.
            pubmed: 1429587
          18. Holden P., Meadows R.S., Chapman K.L., Grant M.E., Kadler K.E., Briggs M.D.. Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family.. J. Biol. Chem. 2001;276:6046–6055.
            pubmed: 11087755
          19. Rosenberg K., Olsson H., Mörgelin M., Heinegård D.. Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen.. J. Biol. Chem. 1998;273:20397–20403.
            pubmed: 9685393
          20. Halász K., Kassner A., Mörgelin M., Heinegård D.. COMP acts as a catalyst in collagen fibrillogenesis.. J. Biol. Chem. 2007;282:31166–31173.
            pubmed: 17716974
          21. Smith R.K.W., Zunino L., Webbon P.M., Heinegård D.. The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load.. Matrix Biol. 1997;16:255–271.
            pubmed: 9501326
          22. Södersten F., Ekman S., Eloranta M.-L., Heinegård D., Dudhia J., Hultenby K.. Ultrastructural immunolocalization of cartilage oligomeric matris protein (COMP) in relation to collagen fibrils in the equine tendon.. Matrix Biol. 2005;24:376–385.
            pubmed: 16005620
          23. Kasashima Y., Takahashi T., Birch H.L., Smith R.K.W., Goodship A.E.. Can exercise modulate the maturation of functionally different immature tendons in the horse?. J. Appl. Physiol. 2008;104:416–422.
            pubmed: 18079264
          24. Smith M.R.W., Wright I.M., Minshall G.J., Verheyen K., Heinegård D., Smith R.K.W.. Increased cartilage oligomeric matrix protein concentrations in equine digital flexor tendon sheath synovial fluid predicts intrathecal tendon damage.. Vet. Surg. 2011;40:54–58.
            pubmed: 21077920
          25. Goodship A.E., Birch H.L., Wilson A.M.. The pathobiology and repair of tendon and ligament injury.. Vet Clin. North Am. Equine Pract. 1994;10:323–349.
            pubmed: 7987721
          26. Cetti R., Junge J., Vyberg M.. Spontaneous rupture of the Achilles tendon is preceded by widespread and bilateral tendon damage and ipsilateral inflammation: A clinical and histopathologic study of 60 patients.. Acta Orthop. Scand. 2003;74:78–84.
            pubmed: 12635798
          27. Riley G.. Tendinopathy – From basic science to treatment.. Rheumatology. 2008;4:82–89.
            pubmed: 18235537
          28. Wilson A.M., Goodship A.E.. Exercise-induced hyperthermia as a possible mechanism for tendon degeneration.. J. Biomechanics. 1994;27:899–905.
            pubmed: 8063840
          29. Smith R.K.W., Birch H.L., Goodman S., Heinegård D., Goodship A.E.. The influence of ageing and exercise on tendon growth and degeneration—Hypotheses for the initiation and prevention of strain-induced tendinopathies.. Comp. Biochem. Physiol. A Mol. Intergr. Physiol. 2002;133:1039–1050.
            pubmed: 12485691
          30. Jones A.J., Bee J.A.. Age- and position-related heterogeneity of equine tendon extracellular matrix composition.. Res. Vet. Sci. 1990;48:357–364.
            pubmed: 2113705
          31. Birch H.L., Bailey A.J., Goodship A.E.. Macroscopic ‘degeneration’ of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition.. Equine Vet. J. 1998;30:534–539.
            pubmed: 9844973
          32. Birch H.L., Bailey J.V.B., Bailey A.J., Goodship A.E.. Age-related changes to the molecular and cellular components of equine flexor tendons.. Equine Vet. J. 1999;31:391–396.
            pubmed: 10505954
          33. Cherdchutham W., Becker C., Smith R.K.W., Barneveld A., van Weeren P.R.. Age-related changes and effect of exercise on the molecular composition of immature equine superficial digital flexor tendons.. Equine Vet. J. 1999;31(Suppl.):86–94.
            pubmed: 10999666
          34. Cherdchutham W., Becker C.K., Spek E.R., Voorhout W.F., van Weeren P.R.. Effects of exercise on the diameter of collagen fibrils in the central core and periphery of the superficial digital flexor tendon in foals.. Am. J. Vet. Res. 2001;62:1563–1570.
            pubmed: 11592320
          35. Dahlgren L.A., Brower-Toland B.D., Nixon A.J.. Cloning and expression of type III collagen in normal and injured tendons of horses.. Am. J. Vet. Res. 2005;66:266–271.
            pubmed: 15757126
          36. Williams I.F., McCullagh K.G., Silver I.A.. The distribution of types I and III collagen and fibronectin in the healing equine tendon.. Connective Tissue Res. 1984;12:211–227.
            pubmed: 6478822
          37. Watkins J.P., Auer J.A., Gay S., Morgan S.J.. Healing of surgically created defects in the equine superficial digital flexor tendon: Collagen-type transformation and tissue morphologic reorganization.. Am. J. Vet. Res. 1985;46:2091–2096.
            pubmed: 4062012
          38. Nixon A.J., Dahlgren L.A., Haupt J.L., Yeager A.E., Ward D.L.. Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis.. Am. J. Vet. Res. 2008;69:928–937.
            pubmed: 18593247
          39. Williams I.F., McCullagh K.G., Goodship A.E., Silver I.A.. Studies on the pathogenesis of equine tendonitis following collagenase injury.. Res. Vet. Sci. 1984;36:326–338.
            pubmed: 6087432
          40. Watts A.E., Nixon A.J., Yeager A.E., Mohammed H.O.. A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis.. Equine Vet. J. 2012;44:576–386.
          41. Eriksen H.A., Pajala A., Leppilahti J., Risteli J.. Increased content of type III collagen at the rupture site of human Achilles tendon.. J. Orthop. Res. 2002;20:1352–1357.
            pubmed: 12472252
          42. Jozsa L., Kannus P.. Histopathological findings in spontaneous tendon ruptures.. Scand. J. Med. Sci. Sports. 1997;7:113–118.
            pubmed: 9211612
          43. Dahlgren L.A., Mohammad H.M., Nixon A.J.. Temporal expression of growth factors and matrix molecules in healing tendon lesions.. J. Orthop. Res. 2005;23:84–92.
            pubmed: 15607879
          44. Crovace A., Lacitignola L., Francioso E., Rossi G.. Histology and immunohistochemistry study of ovine tendon grafted with cBMSCs and BMMNCs after collagenase-induced tendinitis.. Vet. Comp. Orthop. Traumatol. 2008;21:329–336.
            pubmed: 18704239
          45. Maffulli N., Ewen S.W., Waterston S.W., Reaper J., Barrass V.. Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing.. Am. J. Sports Med. 2000;28:499–505.
            pubmed: 10921640
          46. Farina G., Lemaire R., Korn J.H., Widom R.L.. Cartilage oligomeric matrix protein is over expressed by scleroderma dermal fibroblasts.. Matrix Biol. 2006;25:213–222.
            pubmed: 16520029
          47. Hesselstrand R., Kassner A., Heinegård D., Saxne T.. COMP: A candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker.. Ann. Rhem. Dis. 2008;67:1242–1248.
            pubmed: 18065498
          48. Dart A.J., Dart C.M., Dudhia J., Perkins N., Canfield P., Smith R.K.. A preliminary study on the effect of wounding on transforming growth factor-β1 and cartilage oligomeric matrix protein concentrations in the skin of horses.. Vet. Surg. 2011;40:59–65.
            pubmed: 21062324