A new study published in BMB Reports investigated the effects of physalin A, B, D, and F on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL).

Here, biological functions of different physalins were first predicted using an in silico bioinformatic tool (BATMAN-TCM). Thereafter, cell viability and cell apoptosis rate were tested to analyze the cytotoxicity of different physalins. Additionally, the inhibitory effects of physalin D on osteoclast maturation and function were confirmed by immunostaining of F-actin and a pit-formation assay.

It was observed that physalin D has the best selectivity index (SI) among all analyzed physalins. 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). Interestingly, physalin D treatment is known to rescue bone microarchitecture, prevent bone loss and restore bone strength.

The results suggested that physalin D inhibits RANKL-induced osteoclastogenesis and bone loss via suppressing the PLCγ2-CaMK-CREB pathway.

Source: BMB Reports. 2020 Jan 21. pii: 4665