Magnolol Inhibits Osteoclast Differentiation via Suppression of RANKL Expression

Abstract

Magnolol, a compound from the traditional Korean herb Magnolia sp., has been exhaustively investigated as a therapeutic agent against several diseases including systemic and local inflammation. We examined the effects of magnolol on osteoclastic differentiation associated with inflammation. Magnolol markedly reduced interleukin (IL)-1-induced osteoclast formation in co-cultures of murine osteoblasts and bone marrow cells, whereas it had no effect on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in bone marrow macrophage cultures. In osteoblasts, magnolol markedly inhibited both the up-regulation of RANKL expression and the production of prostaglandin E2 (PGE2) in response to IL-1 treatment. Addition of exogenous PGE2 reversed the inhibitory effects of magnolol on IL-1-induced RANKL expression in osteoblasts and osteoclast formation in co-cultures. Magnolol inhibited IL-1-induced PGE2 production, at least in part by suppressing cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that magnolol inhibits IL-1-induced RANKL expression in osteoblasts through suppression of COX-2 expression and PGE2 production, resulting in inhibition of osteoclast differentiation in co-cultures.

Isoflavone‐enriched soybean leaves attenuate ovariectomy‐induced osteoporosis in rats by anti‐inflammatory activity

“…Because osteoclastogenesis is dependent upon RANKL‐induced NFκB activity, selective inhibition of NFκB might prevent osteoclast differentiation 29 . COX‐2 can regulate osteoclast activity, and inhibitors of COX‐2 can effectively suppress OVX‐induced bone loss by decreasing resorptive activity 30 . In the absence of estrogen, activated T‐cells can promote osteoclast recruitment, differentiation, and prolonged survival via IL6 ; elevated IL6 levels have been observed in the OVX mice 16 .…”

“…29 COX-2 can regulate osteoclast activity, and inhibitors of COX-2 can effectively suppress OVX-induced bone loss by decreasing resorptive activity. 30 In the absence of estrogen, activated T-cells can promote osteoclast recruitment, differentiation, and prolonged survival via IL6; elevated IL6 levels have been observed in the OVX mice. 16 The IL6 inhibition can prevent the increase of osteoclast cells in trabecular bones of OVX mice.…”

Pharmacology, Toxicity, Bioavailability, and Formulation of Magnolol: An Update

“…In RANKL-induced RAW 264.7 macrophages, MG (75–150 μM) decreased osteoclast differentiation, tartrate-resistant acid phosphatase activity of differentiated cells, and resorption pit area caused by osteoclasts in a concentration-manner ( Lu et al, 2013 ). MG (10 μM) inhibited IL-1-induced RANKL expression and osteoclast differentiation by suppressing COX-2 expression and PGE2 production ( Hwang et al, 2018 ). MG (2.5–20 μM) attenuated RANKL-induced osteoclast differentiation by suppressing MAPK/c-fos/AP-1 and NF-κB signaling, inhibiting ROS production, and increasing HO-1 expression ( Lu et al, 2015a ).…”

Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca2+ signalling and oxidative stress

“…Achyranthes bidentata polysaccharide, berberine sulphate, nitidine chloride, artesunate and so on were also found to be potential therapeutic candidates for the prevention or treatment of osteoporosis . Other studies also investigated the osteoporotic effects of compounds such as magnolol and polysaccharides …”

“…[20][21][22][23] Other studies also investigated the osteoporotic effects of compounds such as magnolol and polysaccharides. [24][25][26][27][28] As one of BNPs, the compound of Asperpyrone A was isolated from Aspergillus niger with various biological activities including antitumour, antimicrobial and antioxidant. 10,11 Its effects on attenuating RANKL-induced osteoclast formation were identified by our F I G U R E 5 Asperpyrone A suppresses NF-κB signalling pathway.…”