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ADAMTS5 is required for biomechanically‐stimulated healing of murine tendinopathy
Author(s) -
Bell Rebecca,
Li Jun,
Shewman Elizabeth F.,
Galante Jorge O.,
Cole Brian J.,
Bach Bernard R.,
Troy Karen L.,
Mikecz Katalin,
Sandy John D.,
Plaas Anna H.,
Wang Vincent M.
Publication year - 2013
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22398
Subject(s) - tendinopathy , aggrecan , chondrogenesis , extracellular matrix , achilles tendon , tendon , chemistry , mechanotransduction , in vivo , medicine , anatomy , pathology , microbiology and biotechnology , osteoarthritis , cartilage , biology , articular cartilage , biochemistry , alternative medicine
A recently developed murine model of tendinopathy, induced by TGF‐β1 injection, has been used to examine the reparative capacity of tendinopathic Achilles in Adamts5 − / − mice. After TGF‐β1 injection and 2 weeks of treadmill exercise, the Achilles from Adamts5 −/− mice exhibited a reduction in maximum tensile stress of approximately 60%. However, in contrast to wild type mice previously characterized by this model, Adamts5 −/− mice subjected to further treadmill exercise were unable to reverse this biomechanical deficit. This nonreparative phenotype was accompanied by a major deficiency, relative to wild‐type, in expression of Col1a1 and Col3a1 and an abnormally elevated expression of a wide range of integrins. In addition, the tendinopathic Adamts5 −/− mice showed a persistent accumulation of chondrogenic cells in the tendon body and an aggrecan‐rich fibrocartilaginous matrix within disorganized collagen fiber bundles. Moreover, consistent with the compromised biomechanical properties of the Achilles in the Adamts5 −/− mice, in vivo gait analysis revealed a strong trend ( p = 0.07) towards increased swing time of the injected limb in Adamts5 −/− relative to wild‐type mice. These findings demonstrate that a deficiency in ADAMTS5 promotes a chondrogenic response to TGF‐β1 injection that is not reversed by treadmill exercise. Hence, repair of biomechanically compromised tendons exhibiting midsubstance chondroid accumulation requires ADAMTS5. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1540–1548, 2013