Loss of MEF2C expression in osteoclasts leads to a sex-specific osteopenic phenotype

Abstract

Myocyte specific enhancement factor 2C (Mef2c) is a transcription factor studied in the development of skeletal and smooth muscles. Bone resorption studies have exhibited that reduced expression of Mef2c contributes to osteopetrosis and dysregulation of pathological bone remodeling. Our current study aims to determine how Mef2c contributes to osteoclast differentiation and to analyze the skeletal phenotype of Mef2c-cKO mice (Cfms-cre;Mef2cfl/fl). qRT-PCR and western blot demonstrated that Mef2c expression is highest during the early days of osteoclast differentiation. Osteoclast genes, including c-Fos, c-Jun, Dc-stamp, Cathepsin K, and Nfatc1, had a significant reduction in expression along with a reduction in osteoclast size. Despite reduced CTX activity, female Mef2c cKO mice were osteopenic with decreased bone formation as determined by P1NP ELISA. There was no difference between male WT and Mef2c-cKO mice. Our results suggest Mef2c is critical for osteoclastogenesis, and its dysregulation leads to a sex-specific osteopenic phenotype.