RANKL-induced osteoclastogenesis is suppressed by 4-O-methylhonokiol in bone marrow-derived macrophages

다국어 초록 (Multilingual Abstract)

Magnolol, honokiol, and obovatol are wellknown bioactive constituents of the bark of Magnoliaofficinalis and have been reported to have beneficial effectsin various diseases. We recently isolated a novel activecompound, 4-O-methylhonokiol (4-O-MH) from the ethanolextract of M. officinalis, which was previously reportedto have pharmacological effects including anti-inflammatory,anti-oxidative, and anti-aging activities. Here, weexamined the pharmacological properties of 4-O-MH onosteoblast (bone-forming cells) and osteoclast (bone-resorbingcells) differentiation, and its underlying signalingpathways in primary cultured pre-osteoblasts and bonemarrow macrophages. Our results showed that 4-O-MH didnot affect cell viability in pre-osteoblasts and did notinfluence osteoblast differentiation and mineralized noduleformation, as assessed by alkaline phosphatase activity andAlizarin red staining. However, 4-O-MH significantlyinhibited TRAP-positive multinuclear osteoclasts andF-actin ring formation during Receptor activator of NF-jBligand (RANKL)-mediated osteoclastogenesis withoutcytotoxicity. In addition, 4-O-MH suppressed RANKL-inducedcritical factors (c-Fos, NF-ATc1, TRAP, and ITB3)for osteoclast differentiation and function. Furthermore,RANKL-mediated signaling, including ERK1/2, AKT, andNF-kB pathways was attenuated by 4-O-MH. Takentogether, 4-O-MH has an inhibitory role in RANKL-mediatedosteoclastogenesis but not osteoblast differentiation,and our findings also suggest that 4-O-MH is a potentialtherapeutic agent for bone-destructive diseases such asosteoporosis, alveolar bone resorption, and osteoarthritis.

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