OA is an inherently complicated disease, with accumulating evidence to suggest inflammation heavily contributes to the disease process. This understanding presents the OA research community with many challenges, and opportunities, to understand the overall disease pathology. In accordance with the NIAMS mission, this proposal targets not only the broader understanding of inflammation in OA progression, but also targets potential therapies for OA. Specifically, this proposal aims to identify (i) MC involvement in OA inflammation throughout the disease process and (ii) if MCs modulate cross-talk with other key effector cells present within the joint. In the future, we will determine whether MC phenotype can be modulated to be anti-inflammatory via IL-33 signaling. Completion of this work will not only further characterize potential contributors to OA pathogenesis, but provide research into potential, novel treatment options for OA, supporting the NIAMS mission.