Elucidating the role of RBM5 in osteoclastogenesis: a novel potential therapeutic target for osteoporosis

Author:

Zhang Yuyang,Chen Xue,Xiao Yuan,Mei Yibo,Yang Tong,Li Dongchen,Wang Xiaohui,Yang Hao,Huang Dageng,Hao Dingjun

Abstract

AbstractOsteoporosis is a prevalent bone disease with multigene involved, and the molecular mechanisms of its pathogenesis are not entirely understood. This study aims to identify novel key genes involved in osteoporosis to discover potential pharmacological targets. We analyzed three microarray datasets and identified four differentially expressed genes. The LASSO model indicated that RNA-binding motif protein 5 (RBM5) is associated with osteoporosis and is a potential drug target. We conducted the Spearman correlation analysis and found 52 genes that were significantly related to RBM5. Enrichment analysis showed that these genes were primarily involved in RNA splicing and osteoclast differentiation pathways. By using lentivirus-based shRNA, we successfully knocked down RBM5 expression in RAW264.7 cell line, which showed that RBM5 knockdown significantly impaired their differentiation potential to mature osteoclasts and significantly inhibited bone-resorbing activity. RT-qPCR analyses revealed the expression of osteoclastogenesis marker genes was downregulated along with RBM5 expression. These findings suggest that RBM5 plays a crucial role in the pathogenesis of osteoporosis and provides a new potential pharmacological target.

Funder

National Natural Science Foundation of China

Shaanxi Provincial Key Research and Development Project

Scientific Research Project of Xi 'an Health Commission

Publisher

Springer Science and Business Media LLC

Subject

Orthopedics and Sports Medicine,Rheumatology

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