title: Impaired biomechanical properties correlate with neoangiogenesis as well as VEGF and MMP-3 expression during rat patellar tendon healing.
abstract: Recent studies reveal an important role of vascular endothelial growth factor (VEGF)-induced angiogenesis in degenerative tendon diseases. The way how VEGF influences mechanical properties of the tendons is not well understood yet. We here hypothesized that tendinopathy results in a hypoxia-mediated stimulation of VEGF and that the mechanical stability of the tendon is impaired in an angiogenic process by VEGF-induced matrix metalloproteinases (MMPs). A modified in situ freezing model of patellar tendon was used to create a tendinopathy. 0, 7, 14, and 28 days post-surgical animals were sacrificed and patellar tendons were dissected for biomechanical and immunohistochemical analysis. Native tendons were used as controls. Immunohistochemical staining revealed a peak in HIF-1α stabilization immediately after surgery. Both VEGF and MMP-3 were increased 7 days after surgery. Angiogenesis was also abundant 7 days after surgery. In contrast, biomechanical stability of the tendon was decreased 7 days after surgery. The current results reveal a time-dependent correlation of HIF-1/VEGF-induced and MMP-3-supported angiogenesis with decreased biomechanical properties during tendon healing. The therapeutical modulation of neoangiogenesis by influencing the level of VEGF and MMP-3 might be a promising target for new approaches in degenerative tendon diseases. 30:1952-1957, 2012.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, WWU Muenster, Germany.
authors.forename: Hacer
authors.initials: H
authors.lastname: Sahin
authors.forename: Nancy
authors.initials: N
authors.lastname: Tholema
authors.forename: Wolf
authors.initials: W
authors.lastname: Petersen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raschke
authors.forename: Richard
authors.initials: R
authors.lastname: Stange
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D017847:Patellar Ligament / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D052256:Tendinopathy / Q000473:pathology; D013710:Tendons / Q000473:pathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D019278:Matrix Metalloproteinase 3