The health of the musculoskeletal connective tissues of our body (cartilage, tendons, ligaments) is highly dependent on the ability of their cells to continuously maintain or repair the tissue structure. Surprisingly, there is still a limited understanding of why these tissues are able to survive so remarkably well for many decades in young individuals as well as why the tissue is more likely to degenerate in older individuals or those exposed to abnormal joint activities (e.g., athletes, those with physically intensive occupations). This project investigates the existence of an intriguing molecular mechanism that may account for the ability of musculoskeletal tissues to protect themselves, even when faced with the challenging mechanical environment of intense physiologic joint activity. The project will examine the ability of mechanical joint activity to activate, or turn on, a powerful signaling molecule called transforming growth factor beta (TGF-b) that resides inside all musculoskeletal tissues in a latent (inactive) form. This TGF-b activation, in turn, signals cells to generate more tissue proteins, leading to a critical, need-based repair response. This mechanism may explain the resilience of musculoskeletal tissues in young individuals as well as the degeneration that comes with aging or excessive activity. This project expands upon the PI?s track record of promoting research training for under-represented students at the undergraduate and graduate levels. Further, the research will be incorporated into education outreach modules that promote the field of mechanobiology to under-represented K-12 student groups.
The TGF-b-mediated mechanobiological repair mechanism will be examined in an in vitro model, consisting of the long-term mechanical stimulation of explanted tissues of bovine articular cartilage. Using this model, the project will: 1) measure the activation rate of latent TGF-b in response to varying physiologically appropriate mechanical loading regimens; and 2) assess the role of mechanobiological TGF-b activation in preserving the long-term integrity of articular cartilage. The in vitro model will then be expanded to utilize human articular cartilage explants of varying age ranges to assess the potential efficacy loss of this mechanism with aging. This work can greatly expand our knowledge of the factors that lead to musculoskeletal degenerative disorders and potentially advance the development of unique tissue preservation or repair strategies
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
