SUMMARY

Osteoarthritis (OA) is the most common degenerative joint disease, which according to the center for disease control (CDC), affects nearly 30 million people in the United States. The disease is characterized by joint inflammation, which leads to chondrocyte apoptosis, cartilage matrix degradation, loss of joint function, and eventually total knee replacement. 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. Therefore, an unmet medical demand exists for development of tissue-engineering strategies to promote articular cartilage repair and regeneration to treat OA. 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 overall objective of this work was to prevent degeneration of articular cartilage through the development of a 24R,25(OH)2D3 based therapy, enhancing chondrocyte survival and cartilage repair. The central hypothesis was that 24R,25(OH)2D3 has therapeutic effects on osteoarthritic articular chondrocytes, reducing cell apoptosis and factors contributing to joint inflammation and cartilage degradation, thus promoting articular cartilage repair and regeneration.