Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/surv
June 28th, 2008 | by admin |Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling.
ABSTRACT: INTRODUCTION: Subchondral bone alterations represent an essential component of osteoarthritis (OA). Modifying the abnormal subchondral bone metabolism may be indicated to treat OA. We investigated the effect of diacerein and rhein on the changes occurring in subchondral bone during OA. To this end, we determined the drugs\’ effects on MMP-13 synthesis on subchondral bone and on the osteoblast signalling pathways. In osteoclasts, we studied MMP-13 and cathepsin K production, as well as cell differentiation, proliferation and survival. METHODS: The effect of diacerein/rhein on the production of subchondral bone MMP-13 was determined by ELISA. Signalling pathways were evaluated on osteoblasts by Western blot. Osteoclast experiments were performed using the pre-osteoclastic cells, Raw 264.7. Osteoclast MMP-13 and cathepsin K activities were determined by specific bioassays and differentiation of these cells quantified by TRAP staining. RESULTS: Diacerein and rhein reduced in a dose-dependent manner the IL-1beta-induced MMP-13 production in OA subchondral bone. This effect occurred through the inhibition of ERK1/2 and p38. In osteoclasts, they significantly reduced the activity of MMP-13 and cathepsin K. Moreover, these drugs effectively blocked the IL-1beta effect on the osteoclast differentiation process and the survival of mature osteoclasts. CONCLUSIONS: Altogether these data suggest that diacerein/rhein could impact the abnormal subchondral bone metabolism in OA by reducing the synthesis of resorptive factors and osteoclast formation.
Boileau C, Kwan Tat S, Pelletier JP, Cheng S, Martel-Pelletier J.