RANKL-induced osteoclastogenesis is suppressed by 4-O-methylhonokiol in bone marrow-derived macrophages
- Authors
- Park, Kyung-Ran; Kim, Ji-Youn; Kim, Eun-Cheol; Yun, Hyung-Mun; Hong, Jin Tae
- Issue Date
- Aug-2017
- Publisher
- PHARMACEUTICAL SOC KOREA
- Keywords
- Magnolia officinalis; 4-O-methylhonokiol; Osteoblast; Osteoclast; RANKL
- Citation
- ARCHIVES OF PHARMACAL RESEARCH, v.40, no.8, pp.933 - 942
- Journal Title
- ARCHIVES OF PHARMACAL RESEARCH
- Volume
- 40
- Number
- 8
- Start Page
- 933
- End Page
- 942
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5852
- DOI
- 10.1007/s12272-017-0932-z
- ISSN
- 0253-6269
- Abstract
- Magnolol, honokiol, and obovatol are well known bioactive constituents of the bark of Magnolia officinalis and have been reported to have beneficial effects in various diseases. We recently isolated a novel active compound, 4-O-methylhonokiol (4-O-MH) from the ethanol extract of M. officinalis, which was previously reported to have pharmacological effects including anti-inflammatory, anti-oxidative, and anti-aging activities. Here, we examined the pharmacological properties of 4-O-MH on osteoblast (bone-forming cells) and osteoclast (bone-resorbing cells) differentiation, and its underlying signaling pathways in primary cultured pre-osteoblasts and bone marrow macrophages. Our results showed that 4-O-MH did not affect cell viability in pre-osteoblasts and did not influence osteoblast differentiation and mineralized nodule formation, as assessed by alkaline phosphatase activity and Alizarin red staining. However, 4-O-MH significantly inhibited TRAP-positive multinuclear osteoclasts and F-actin ring formation during Receptor activator of NF-kappa B ligand (RANKL)-mediated osteoclastogenesis without cytotoxicity. In addition, 4-O-MH suppressed RANKL-induced critical factors (c-Fos, NF-ATc1, TRAP, and ITB3) for osteoclast differentiation and function. Furthermore, RANKL-mediated signaling, including ERK1/2, AKT, and NF-kB pathways was attenuated by 4-O-MH. Taken together, 4-O-MH has an inhibitory role in RANKL-mediated osteoclastogenesis but not osteoblast differentiation, and our findings also suggest that 4-O-MH is a potential therapeutic agent for bone-destructive diseases such as osteoporosis, alveolar bone resorption, and osteoarthritis.
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