Chondroid metaplasia is a long-term consequence of tendinopathy induced by both stress-deprivation and over-stress: temporal differences in molecular pathology

Introduction Degeneration and tearing of rotator cuff tendon causes significant morbidity in our ageing population. While conservative treatment is favored, there are no current drug therapies to specifically treat cuff or other tendon injuries so surgical repairs are common (over 14,000 annually in Australia). Unfortunately half of these repairs fail within 12 months. The poor management options and outcomes for rotator cuff disorders are driven by the degenerative changes in the tendon that both precede and lead to tearing, and result from altered loading of tendon after partial rupture. Preand post-rupture changes are difficult to study in humans due to unknown temporality of injury. An animal model of shoulder tendon injury induced by partial infraspinatus tendon transection, has been recently established in our laboratories [1]. In this model the effects of both overstress (OS) and stress deprivation (SD) can be simultaneously evaluated in different regions of the one tendon. At 4 weeks after stress alteration, spatial changes in collagen, proteoglycan and catabolic ADAMTS and MMP enzymes were demonstrated [1]. We now report the temporal changes in pathology, proteoglycan localisation and gene expression changes for up to a year after induction of tendinopathy. These studies aimed to determine whether the early pathology resolves or progresses and the molecular changes that underlie these temporal changes.