RORβ modulates a gene program that is protective against articular cartilage damage

Abstract

Osteoarthritis (OA) is the most prevalent chronic joint disease which increases in frequency with age eventually impacting most people over the age of 65. OA is the leading cause of disability and impaired mobility, yet the pathogenesis of OA remains unclear. Treatments have focused mainly on pain relief and reducing joint swelling. Currently there are no effective treatments to slow the progression of the disease and to prevent irreversible loss of cartilage. Here we demonstrate that stable expression of ROR{beta} in cultured cells results in alteration of a gene program that is supportive of chondrogenesis and is protective against development of OA. Specifically, we determined that ROR{beta} regulates the balance of FGFRs signaling on FGFR1/FGFR3 that ERK1/2-MAPK signaling was suppressed by FGFR1(cartilage destruction) and AKT signaling was enhanced by FGFR3 (cartilage protection). These results suggest a critical role for ROR{beta} in chondrogenesis and suggest that identification of mechanisms that control the expression of ROR{beta} in chondrocytes could lead to the development of disease modifying therapies for the treatment of OA.