Committee:

Barbara Boyan, Ph.D., Advisor
Zvi Schwartz, DMD, Ph.D.
Julia Babensee, Ph.D.
Manu Platt, Ph.D.
David Hart, PH.D.

Osteoarthritis (OA) is a degenerative disease characterized by joint inflammation, which leads to cartilage matrix degradation, chondrocyte apoptosis, and progressive cartilage degeneration. Current drug therapies aim to ease pain and reduce local inflammation; however, no drug exists that effectively alleviates the disease condition without significant side effects that are typical to anti-inflammatory drugs. 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] is an attractive option for articular cartilage repair because of its anti-apoptotic properties in cartilage cells. The long-term goal of this work is to develop a 24R,25(OH)2D3-based drug therapy for osteoarthritis prevention and articular cartilage repair. The aim of present thesis is to evaluate the use of 24R,25(OH)2D3 as a therapy to prevent the progression of osteoarthritis in in vitro and in vivo OA models, and to examine the association of vitamin D3 metabolite levels and severity of osteoarthritis in humans.