The role of Mef2a in mice osteoclasts
Osteoporosis, a common disorder affecting 10 million Americans primarily affects postmenopausal women due to their decrease in estrogen exprression. Osteoporosis results in bone loss due to an increase in osteoclasts. Current treatments for osteoporosis include hormone treatment and bisphosphonates but these treatments can have adverse side effects. Understanding the exact intracellular mechanism by which osteoclast differentiation occurs may lead to the development of a safer alternative. Skeletal bone is shaped by two cells in the human body, osteoclasts and osteoblasts. Bone resorbing osteoclasts are inhibited by the presence of estrogen through an intracellular cascade. Previous data from the Mansky lab suggests that Mef2a, a transcription factor in osteoclasts, is regulated by estrogen. However, the specific intracellular effects of estrogen in osteoclasts are currently not well understood. Our data demonstrates that estrogen is a direct regulator of Mef2a expression, which in turn regulates Rcan2, a protein present in osteoclasts. Rcan2 has long been known to negatively regulate the entrance of NFATC1, the master osteoclast transcription factor, into the nucleus. Additionally, we determined changes in Hdac9 expression which suggests that either MEF2A and/or estrogen regulate expression of Hdac9. We hypothesize that MEF2A and RCAN2 work in opposition to regulate osteoclast differentiation. This data will help us better understand a mechanism by which estrogen decreases osteoclastogenesis.