T63 inhibits osteoclast differentiation through regulating MAPKs and Akt signaling pathways

European Journal of Pharmacology
Xiao-Li ZhaoZhen Wang

Abstract

Inhibition of excessive osteoclast differentiation and activity is a valid approach for the treatment of osteoporosis. T63 is a small-molecule compound identified from a high throughput screening based on RUNX2 transcriptional activity, and has been reported to stimulate osteoblast formation. However, whether the compound has any effect on osteoclast differentiation remains unknown. Here, we examined the in vitro effect of T63 on osteoclastogenesis. T63 was found to inhibit the number of TRAP-positive cells in an osteoblast-osteoclast co-culture system, and inhibited Rankl expression in the preosteoblast MC3T3-E1 cells. The compound also directly suppressed RANKL-induced osteoclast differentiation in both dose- and time-dependent manner, as evidenced by the decrease of TRAP activity, F-actin formation and osteoclastogenesis-related genes expression in RAW264.7 cells. Moreover, pretreatment with T63 markedly decreased the activation of mitogen-activated protein kinases and Akt, both of which are positively involved in the regulation of osteoclastogenesis. Collectively, our findings suggest T63 has a protective effect against bone loss by inhibiting bone resorption. Its regulatory effect on bone metabolism makes the compound a mo...Continue Reading

Citations

Dec 9, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Xiaoli ZhaoZhen Wang
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ga-Ram KimGil-Saeng Jeong

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