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http://dx.doi.org/10.5483/BMBRep.2020.53.3.147

Physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via regulating calcium signaling  

Ding, Ning (Department of Blood Purification, General Hospital of Shenyang Military Area Command)
Lu, Yanzhu (Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University))
Cui, Hanmin (Department of Blood Purification, General Hospital of Shenyang Military Area Command)
Ma, Qinyu (Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University))
Qiu, Dongxia (Department of Blood Purification, General Hospital of Shenyang Military Area Command)
Wei, Xueting (Department of Blood Purification, General Hospital of Shenyang Military Area Command)
Dou, Ce (Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University))
Cao, Ning (Department of Blood Purification, General Hospital of Shenyang Military Area Command)
Publication Information
BMB Reports / v.53, no.3, 2020 , pp. 154-159 More about this Journal
Abstract
We investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor κB 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 RANKL-evoked 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.
Keywords
Bone; Calcium Signaling; Osteoclast; Osteoporosis; Physalin;
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