ArticleBiochemical genetics2026
Myocyte-Specific Enhancer Factor 2A Potentiates Osteoclastic Differentiation in Osteoporosis by Inducing Endothelin Receptor Type A.
Article in Biochemical genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Activation of endothelin receptor type A (EDNRA) has been revealed to induce osteoclastic bone resorption during orthodontic treatment. In this study, we investigated the mechanisms by which EDNRA potentiates osteoclastic differentiation in ovariectomy (OVX)-induced mice with osteoporosis (OP)-like symptoms. The effects of knocking down EDNRA on OP in mice were observed using micro-CT, HE staining, TRAP staining, RT-qPCR, and immunoblotting. The effects of the knockdown of EDNRA in osteoclastic differentiation of bone marrow macrophages (BMs) were investigated by TRAP staining, F-actin staining, RT-qPCR, and immunoblotting. EDNRA was highly expressed in osteoporotic mice, and the knockdown of EDNRA in vivo alleviated osteoporotic phenotypes in OVX-induced mice by inhibiting osteoclast differentiation. BMs with EDNRA knockdown showed repressed MMP1, MMP8, and RANKL protein expression and Nfatc1, Ctsk, C-fos, and Trap mRNA expression. Myocyte-specific enhancer factor 2A (MEF2A) transcriptionally promoted EDNRA expression by binding to the EDNRA promoter. Silencing of MEF2A exerted the same anti-osteoporotic effects, which were reversed by overexpression of EDNRA. Altogether, our findings highlight that MEF2A knockdown alleviates loss of bone mass in the OVX-induced mice by suppressing osteoclast differentiation via inhibition of EDNRA transcription.
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