Transcriptome Analysis Reveals That Abeliophyllum distichum Nakai Extract Inhibits RANKL-Mediated Osteoclastogenensis Mainly through Suppressing Nfatc1 Expression

Abstract

<i>Abeliophyllum distichum</i> Nakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed that <i>A. distichum</i> extract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity of <i>A. distichum</i> extract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves of <i>A. distichum</i>, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-κB 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 of <i>A. distichum</i> efficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.