The Role of MEF2A and Estrogen in Osteoclast Differentiation

Abstract

Introduction: Preliminary studies indicate that female mice null for MEF2A expression in osteoclasts have increased bone volume to total volume. Additionally, female mice have bone biomarkers that suggest a decrease in osteoclast activity. In cardiac cells, the MEF2 family of transcription factors along with class IIA HDACs, HDAC9 and HDAC5, were shown to regulate the expression and activity of the estrogen receptor. The purpose of this study is to determine if MEF2A regulates Esr1, the gene for ER-alpha in osteoclasts. Methods: For this study, bone marrow cells from WT and Mef2a knockout female mice will be analyzed by qRT-PCR for the expression of Esr1 and Hdac9. The amount of apoptosis by qRT-PCR and caspase 3/7 activity will be measured in WT osteoclasts and osteoclasts null for Mef2a. Unpaired t-test or one-way ANOVA analysis were used to compare the data using Graph-Pad Prism version 8. Results: Esr1 expression was increased in osteoclasts from female mice null for Mef2a compared to WT osteoclasts. Hdac9 expression was significantly decreased in Mef2a null osteoclasts early in the osteoclast differentiation process. Fas and Fas-L expression, as well as caspase 3/7 activity, were not significantly altered in Mef2a null osteoclasts. This data suggests that MEF2A is not regulating osteoclast differentiation through induction of apoptosis. Conclusion: MEF2A expression in osteoclasts suppresses ER-alpha expression in female mice leading to decrease in osteoclast differentiation.