BCAP promotes osteoclast differentiation through regulation of the p38-dependent CREB signaling pathway

Many studies have determined that PI3K-Akt signaling pathways play important roles in osteoclast differentiation and function. In the present study, we investigated the roles of B-cell adaptor for MK (BCAP), which is a P13K binding molecule, in osteoclasts. Overexpression of BCAP in osteoclast precursor cells enhanced osteoclast differentiation induced by tumor necrosis factor alpha (TNF-alpha) as well as receptor activator of nuclear factor kappa B ligand (RANKL). Conversely, osteoclast differentiation mediated by both cytokines was attenuated when BCAP expression was downregulated using small interfering RNA. Notably, BCAP induced Akt activation only -upon stimulation by RANKL, but not by TNF-a. However, BCAP activated p38-dependent cAMP response element-binding protein (CREB) phosphorylation induced by both RANKL and TNF-a. Collectively, we showed that BCAP plays an important role in osteoclast differentiation by regulating the p38-dependent CREB signaling pathway, and that BCAP might be a new therapeutic target for bone diseases. (C) 2017 Elsevier Inc. All rights reserved.