Conditional Loss of MEF2C Expression in Osteoclasts Leads to a Sex-Specific Osteopenic Phenotype

Myocyte enhancement factor 2C (MEF2C) is a transcription factor studied in the development of skeletal and smooth muscles. Bone resorption studies have exhibited that the reduced expression of MEF2C contributes to osteopetrosis and the dysregulation of pathological bone remodeling. Our current study aims to determine how MEF2C contributes to osteoclast differentiation and to analyze the skeletal phenotype of cKO mice (; ). qRT-PCR and Western blot demonstrated that expression is highest during the early days of osteoclast differentiation. Osteoclast genes, including c, , , and , had a significant reduction in expression, along with a reduction in osteoclast size. Despite reduced CTX activity, female cKO mice were osteopenic, with decreased bone formation as determined via a P1NP ELISA, and a reduced number of osteoblasts. There was no difference between male WT and cKO mice. Our results suggest that is critical for osteoclastogenesis, and that its dysregulation leads to a sex-specific osteopenic phenotype.