Role of inorganic polyphosphate in articular cartilage homeostasis

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Articular cartilage is a soft tissue that covers the surfaces of bones in synovial joints. This load-bearing tissue enables low friction movement and distributes forces transmitted through the joint. Cartilage integrity is maintained by tightly regulated mechanisms that balance the breakdown of the tissue and its replacement with newly synthesized biomolecules (homeostasis). Prolonged imbalance between these two processes in response to a changing biological or mechanical environment in the joint has been associated with the onset of osteoarthritis (OA), a group of debilitating joint diseases characterized by the progressive degradation of cartilage that affects more than 3 million Canadians. Over the course of my academic career, I have developed cross-disciplinary expertise in materials engineering and matrix biology as it pertains to cartilage biology and repair. As a new faculty member at the University of Ottawa, I will establish a research program focused on elucidating the dynamic cell-tissue interactions regulating cartilage homeostasis. Understanding these control mechanisms will not only provide a more complete picture of physiological processes that allow tissues to maintain their functions in the body, but also to develop next-generation biomaterials that interface cells with instructive environments, which control specific biological processes. Restoring healthy cartilage using such treatments would improve healthcare practice, as well as recovering quality of life and alleviating the social and economic burdens of OA sufferers in Canada and worldwide.In this application, funding is requested for the first stage of this research program, aimed at evaluating the hypothesis that inorganic polyphosphate (PP), a biomolecule present in the pericellular matrix of articular cartilage, regulates homeostasis. In light of its involvement in a mounting number of fundamental processes in a range of mammalian tissues, there is a critical need to improve our understanding of PP biology. Here, we propose to build on our previous work demonstrating the anabolic effects of PP in articular cartilage to establish the extent of its effects on the balance between anabolic and catabolic processes and to determine its role in tissue remodeling in response to mechanical stimulation. Finally, we will explore the signaling pathways impacted by PP to produce a better understanding of the dynamic interactions between chondrocytes and their pericellular environment.This funding will also support the development of 4 HQP under my guidance. Through their work on these multidisciplinary projects, the graduate students will acquire a variety of technical skills and be provided with opportunities for critical thinking and creativity that will prepare them for a continued career in biomedical engineering.