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

ABSTRACT: 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 C?2 (PLC?2) and thus blocked the downstream activation of Ca2?/calmodulindependent 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 PLC?2-CaMK-CREB pathway. [BMB Reports 2020; 53(3): 154-159].

SUBMITTER: Ding N 

PROVIDER: S-EPMC7118355 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature