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

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 alters the ratio of expression of the FGF receptors FGFR1 (associated with cartilage destruction) and FGFR3 (associated with cartilage protection). Additionally, ERK1/2-MAPK signaling was suppressed and AKT signaling was enhanced. 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.

Automated summary

Osteoarthritis (OA) is a common joint disease that affects the elderly population and is a major cause of disability and impaired mobility. Current treatments focus on pain relief and reducing joint swelling, but there are no effective methods to slow disease progression and prevent cartilage loss. Research suggests that ROR beta plays a critical role in chondrogenesis and identifying mechanisms that control its expression could lead to the development of new therapies for treating OA.