Blockade of 11β-hydroxysteroid dehydrogenase type 1 enzyme inhibits experimental collagenase-induced osteoarthritis

Abstract

Osteoarthritis (OA) is a common cause of functional deterioration in the joints of elderly adults and is a significant burden on the health of the aging population. 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), which converts cortisone to cortisol, is known to contribute to a number of inflammatory diseases. However, the role of 11β-HSD1 in human OA remains unclear. The aim of this study was to identify the effects of the selective 11β-HSD1 inhibitor, BVT-2733, in murine collagenase-induced osteoarthritis (CIOA). CIOA mice were treated with BVT-2733 (100 mg/kg, orally) or control vehicle twice daily for five weeks. Cartilage and bone destruction were subsequently examined. The expression of bone markers and STAT3 phosphorylation in joint tissues were detected using western blot analysis. The concentrations of proinflammatory cytokines were determined by an enzyme-linked immunosorbent assay. Treatment with BVT-2733 attenuated cartilage and bone destruction, and reduced the expression of bone markers and p-STAT3 in the joints of CIOA mice. BVT-2733 also decreased the serum levels of interleukin (IL)-1β, IL-6, IL-17 and vascular endothelial growth factor. In conclusion, the present study showed that BVT-2733 inhibits multiple inflammatory signaling pathways in the joints of CIOA mice, suggesting that 11β-HSD1 inhibition may have therapeutic potential in human OA.