Protein Bcl-xL Prevents Bone Breakdown

To determine the function of Bcl-xL in osteoclasts, the researchers generated mice lacking Bcl-xL only in osteoclasts. As in blood cells, Bcl-xL was shown to promote the survival of osteoclasts. Unexpectedly, however, the mutant mice exhibited marked osteopenia at one year of age. Further analysis indicated that the reduced bone mass was caused by increased osteoclast-mediated bone resorption and identified a potential underlying mechanism. Specifically, Bcl-xL was found to decrease the production of extracellular matrix proteins, which bind cell surface integrin molecules, leading to the activation of c-Src signaling pathways that are already known to promote osteoclast-mediated bone resorption. Thus, in the absence of Bcl-xL, increased production of extracellular matrix proteins leads to increased osteoclast-mediated bone resorption.