Characterizing the effect of BMP2 on osteoclast differentiation and activity

Abstract

Bone is a profoundly dynamic tissue, characterized by continuous remodeling with bone formation by osteoblasts and bone resorption by osteoclasts. Bone morphogenetic proteins (BMPs) are multifunctional cytokines belonging to the TGF-β superfamily involved in numerous molecular cascades and signaling pathways. While BMPs are well known key regulators of osteoblast biology, their role in modulating the differentiation of osteoclasts is not as well known. The goals of this study were to further characterize the role of BMP2 in osteoclast activation by evaluating the expression of BMP receptors and BMP ligands in BMP2;LysM-Cre cKO osteoclasts, and measure the quantity and timing of expression of BMP2 protein by osteoclasts during differentiation. Our results showed that osteoclasts maximally express BMP2 two days after addition of RANKL to in vitro cultures. BMP2 was also detected in media of osteoclast cultures at day 3 after RANKL addition, which correlates with the activation of SMAD1/5/8 signaling in osteoclasts. Though not significant, osteoclasts from Bmp2;LysM-Cre mice demonstrated a trend of increased Rank and c-Fms mRNA expression, decreased Bmpr1a, Bmpr1b, and BmprII mRNA expression, no change in Bmp4 mRNA expression, and a decrease in Bmp6 mRNA expression. These trends will be further investigated in future experiments to evaluate the significance of the role of BMP2 in their expression.