ADAMTS5 is required for biomechanically-stimulated healing of murine tendinopathy.

Abstract

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.