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KMID : 0043320170400080933
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Archives of Pharmacal Research
2017 Volume.40 No. 8 p.933 ~ p.942
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RANKL-induced osteoclastogenesis is suppressed by 4-O-methylhonokiol in bone marrow-derived macrophages
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Park Kyung-Ran
Kim Ji-Youn
Kim Eun-Cheol
Yun Hyung-Mun
Hong Jin-Tae
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Abstract
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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-κB 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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KEYWORD
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Magnolia officinalis, 4-O-methylhonokiol, Osteoblast, Osteoclast, RANKL
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