Professor Buckley receives pilot grant from CMSR

May 11, 2017

sdfProfessor Mark Buckley has received a pilot grant from the Center for Musculoskeletal Research for his research project, "The influence of chondrocyte mechano-protective adaptation on the progression of osteoarthritis.” Osteoarthritis (OA)  – a painful and complex joint disease characterized by progressive degeneration of articular cartilage and surrounding tissues – is among the leading causes of disability in the United States. Yet, there are no FDA-approved treatments proven to stop or reverse OA and preserve joint health, suggesting that novel targets for OA interventions are needed. Though the complete etiology of OA is unknown, aberrant mechanical loads leading to cell death and catabolic activity are thought play a role in this pathology. To maintain homeostasis when confronted by sustained biochemical stimuli, cells have a well-characterized ability to moderate their response to these signals (e.g., through downregulation of a surface receptor). The Buckley lab's preliminary data suggests that chondrocytes can also rapidly moderate their sensitivity to sustained mechanical stimuli (e.g., during ambulation) to prevent cell death or abnormal (pathological) behavior. Hence, it may be possible to prevent or slow OA by enhancing this adaptive phenomenon, which we refer to herein as cytoprotective adaptation to mechanical stimuli (CAMS).

The lab's long-term goal is to develop translatable therapies that protect cartilage from degeneration through stimulation or enhancement of CAMS. To take the next step towards this goal, the objective herein is to rigorously characterize our in vivo cartilage injury model and employ this model to assess how CAMS impacts long-term OA progression. Based on the lab's preliminary data, the central hypothesis is that CAMS slows OA pathogenesis following a traumatic joint injury. The rationale for the proposed study is that identifying CAMS as a chondroprotective cellular process address the need for identification of new and promising targets of OA interventions.