Effect of BMS-582949 treatment on gene expression in osteoclasts

Controlling excessive osteoclastic activity is a promising strategy for many bone disease treatments. Here we report that 10 μM BMS-582949, a clinical p38α inhibitor,dromatically suppresses the osteoclast differentiation in vitro. Our results provide a evidence that BMS-582949 could be a candicdate drug for the therapy of osteolytic diseases. To investigate the function of BMS-582949 in osteoclastogenesis, mouse bone marrow cells from wild-type C57BL/6J mice were extracted and cultured for 3 days. The attached bone marrow-derived macrophages (BMMs) were then scraped, and reseeded in α-MEM medium with 10% FBS, 1% penicillin-streptomycin, 1% L-glutamine, and M-CSF overnight at 37 °C in a humidified atmosphere containing 5% CO2, and then stimulated by 40 ng/ml RNAKL and CM for 3 days in the presence or absence of 10 μM BMS-582949.The media was changed after 3 days. At day 4, total RNAs from matured osteoclasts were extracted using TRIzol reagents and performed subjected to RNA sequencing.