Grant: Operating Grant

Cartilage is one of the few tissues in the body that does not exhibit some level of endogenous repair, in part because of the apparent lack of stem/progenitor cells in this tissue. However, the adjacent synovial membrane is abundant with mesenchymal progenitor cells capable of differentiating into cartilage both in vitro and in vivo. Super-healer (MRL) mice have the unique ability to regenerate tissues (including articular cartilage) without scaring. We hypothesize that intrinsic cartilage regeneration in the super-healer mouse results from (a) increased numbers and chondrogenic potential of progenitor cells located within the joint coupled with (b) decreased Monocyte Chemo-attractant Protein-1 (MCP-1/CCL2) response after injury which prevents further cartilage degeneration, and (c) that these unique regenerative abilities are conferred through reduced p21 expression. The experiments described in this proposal will demonstrate if cartilage regeneration in the MRL mouse is a result of modified endogenous progenitor behaviour, alone or in concert with alterations of the inflammatory response after injury. These results along with future experiments will define a research program that centers on the development of new tissue engineering and/or regenerative medicine approaches for the repair of tissues that demonstrate impaired healing in vivo.