Transcriptome Analysis Reveals ThatAbeliophyllum distichumNakai Extract Inhibits RANKL-Mediated Osteoclastogenensis Mainly through Suppressing Nfatc1 Expression

Abeliophyllum distichumNakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed thatA. distichumextract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity ofA. distichumextract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves ofA. distichum, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-kappa B ligand (RANKL)-induced osteoclast differentiation. Second, our transcriptome analysis revealed that the leaf extract (LE) blocks sets of RANKL-mediated osteoclast-related genes. Third, the LE attenuates the phosphorylation of extracellular signal-related kinase. Finally, treatment with the LE effectively prevents postmenopausal bone loss in ovariectomized mice and glucocorticoid-induced osteoporosis in zebrafish. Our findings show that the extract ofA. distichumefficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.