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KMID : 0624620200530030154
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BMB Reports
2020 Volume.53 No. 3 p.154 ~ p.159
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Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling
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Ding Ning
Lu Yanzhu
Cui Hanmin
Ma Qinyu
Qiu Dongxia
Wei Xueting
Dou Ce
Cao Ning
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Abstract
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We investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor ?B ligand (RANKL). The biological functions of different physalins were first predicted using an in silico bioinformatic tool (BATMAN-TCM). Afterwards, we tested cell viability and cell apoptosis rate to analyze the cytotoxicity of different physalins. We analyzed the inhibitory effects of physalins on RANKL-induced osteoclastogenesis from mouse bone-marrow macrophages (BMMs) using a tartrate-resistant acid phosphatase (TRAP) stain. We found that physalin D has the best selectivity index (SI) among all analyzed physalins. We then confirmed the inhibitory effects of physalin D on osteoclast maturation and function by immunostaining of F-actin and a pit-formation assay. On the molecular level, physalin D attenuated RANKLevoked intracellular calcium ([Ca(2+)](i)) oscillation by inhibiting phosphorylation of phospholipase Cγ2 (PLCγ2) and thus blocked the downstream activation of Ca2＋/calmodulin-dependent protein kinases (CaMK)IV and cAMP-responsive element-binding protein (CREB). An animal study showed that physalin D treatment rescues bone microarchitecture, prevents bone loss, and restores bone strength in a model of rapid bone loss induced by soluble RANKL. Taken together, these results suggest that physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via suppressing the PLCγ2-CaMK-CREB pathway.
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KEYWORD
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Bone, Calcium Signaling, Osteoclast, Osteoporosis, Physalin
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