title: Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture.
abstract: Tendon integrity depends on the extracellular matrix (ECM) metabolism which is regulated by proteolytic enzymes. However, it is unclear which enzymes play a role in tendon rupture. We studied the ECM of 19 ruptured human Achilles tendons, comparing the composition of specimens harvested close to the rupture with specimens harvested from an apparently healthy area in the same tendon. We compared gene expression of collagen Type I, decorin, and versican including enzymes involved in their metabolism as matrix metalloproteases (MMP-2 and -9) and tissue inhibitory of metalloproteinase (TIMP-1 and -2) using real-time PCR, zymography and FACE analysis. We found greater gene expression of proteoglycan core protein decorin and versican, collagen Type I, MMPs and TIMPs in the tendon rupture. Zymography analysis, reflecting expression of enzymatic activity, confirmed the gene expression data at protein level. Carbohydrate content was greater in the macroscopically healthy area than in the ruptured area. In the ruptured area, we found increased core protein synthesis but without the normal glycosaminoglycan production. The tissue in the area of rupture undergoes marked rearrangement at molecular levels and supports the role of MMPs in the pathology.
authors.affiliation: Department of Experimental Biomedical and Clinical Sciences (DSBSC), University of Insubria, Varese, Italy.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Karousou
authors.forename: Mario
authors.initials: M
authors.lastname: Ronga
authors.forename: Davide
authors.initials: D
authors.lastname: Vigetti
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
authors.forename: Nicola
authors.initials: N
authors.lastname: Maffulli
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism*; D000328:Adult; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D058575:Decorin; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012421:Rupture; D013708:Tendon Injuries / Q000235:genetics / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D053675:Versicans / Q000235:genetics
chemical_list: D024042:Collagen Type I; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D053675:Versicans; D019716:Tissue Inhibitor of Metalloproteinase-2; D045726:Metalloproteases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9