Bone Morphogenetic Protein-2 (BMP2) upregulates osteoclast gene expression.

Abstract

Bone Morphogenetic Proteins (BMPs) induce bone formation by osteoblasts, but their direct role in bone resorption by osteoclasts remains to be characterized. Twisted Gastrulation (Twsg1) is a secreted BMP binding protein that inhibits BMPs from binding to their receptors. Mice lacking the Twsg1 gene (Twsg1-/-) exhibit an osteopenic skeletal defect. Previous studies indicate that the osteopenic phenotype in Twsg1-/- mice is due to increased osteoclastogenesis and not due to reduced osteoblast function. This study hypothesizes that treatment of wild-type osteoclasts with BMP2 will increase osteoclast gene expression and that this gene expression will decrease with the addition of the known BMP inhibitor, Noggin. The results of this investigation show that the addition of BMP2 to RANKL upregulates Cathepsin K, Nfatc1, Acp5, DCSTAMP, and ATP6v6d02 gene expression levels. The addition of the more well understood BMP inhibitor, Noggin, downregulates these gene expression levels. These results indicate a possible direct mechanism of action for BMP2 on osteoclast activation.