Abstract
Tendon tissue equilibrium very heavily depends on appropriate mechanical loading within a narrow, and still poorly defined, physiological range. We will present an overview of our recent work on the tendon cell-matrix interactions that drive tissue homeostasis, matrix remodelling and eventual tissue degeneration, and discuss a roadmap for unravelling these mechanically regulated signalling pathways for the development of effective treatment strategies. Our data suggest that tissue damage accumulates in the tendon until “intrinsic repair mechanisms” are overwhelmed. At this point, the metabolic cost of extracellular matrix remodeling exceeds the locally available nutrient supply. We hypothesize that upon reach S43.1 ing this “Metabolic Tipping Point”, the vascular system is recruited along with accompanying nerve supply (and pain) and the tissue enters into a chronic disease state characterized by high matrix turnover and increasingly poor tissue quality. In this paradigm, a delicate mechanically regulated balance exists between recruitment and suppression of the extrinsic vascular system by the resident tendon core cells. Upon injury or damage, this regulation in turn steers the tissue towards either functional remodeling or chronic tendon disease.
