Brain abundant membrane attached signal protein 1 (BASP1) - a novel regulator of osteoclastogenesis

Brain abundant membrane attached signal protein 1 (BASP1) is a membrane localized protein that is present in the growth cones of nerve cells and regulates signal transduction and cytoskeletal organization. It was reported to inhibit megakaryote differentiation upon PMA treatment of a macrophage cell line. Here we report the importance of BASP1 in regulating osteoclastogenesis. We show that BASP1 is significantly downregulated upon RANKL treatment in bone marrow derived macrophages. siRNA- and shRNA-mediated downregulation of BASP1 resulted in significantly increased numbers of osteoclasts. Knockdown of BASP1 significantly increased the induction of osteoclast marker genes Itgb3, Dcstamp, Mmp9, and Ctsk by RANKL and increased the sensitivity of cells towards RANKL driven osteoclastogenesis. In agreement, BASP1-knockdown osteoclasts were larger and more active than control cells. In support of these results, we found that the expression of BASP1 is downregulated in osteoclasts compared to monocyte precursor cells by analyzing previously published single cell transcriptomic data. In conclusion, our results suggest that BASP1 is a novel negative regulator of osteoclastogenesis.