Bcl-xL inhibits the bone-resorbing activity of osteoclasts

The B cell lymphoma 2 (Bcl-2) family member Bcl-xL has a well-characterized antiapoptotic function in lymphoid cells. However, its functions in other cells - including osteoclasts, which are of hematopoietic origin - and other cellular processes remain unknown. The authors of a recent study [1] report an unexpected function of Bcl-xL in attenuating the bone-resorbing activity of osteoclasts in mice. To investigate the role of Bcl-xL in osteoclasts, they generated mice with osteoclast-specific conditional deletion of Bcl-x.

Although the Bcl-x knockout mice grew normally with no apparent morphological abnormalities, they developed substantial osteopenia at 1 year of age, which was caused by increased bone resorption. Bcl-x deficiency increased the bone-resorbing activity of osteoclasts despite their high susceptibility to apoptosis, whereas Bcl-xL overexpression produced the opposite effect. In addition, Bcl-x knockout osteoclasts displayed increased levels of vitronectin and fibronectin expression.

These results suggest that Bcl-xL attenuates osteoclastic bone-resorbing activity through the decreased production of extracellular matrix proteins, such as vitronectin and fibronectin, and thus provides evidence for a novel cellular function of Bcl-xL.

1. Iwasawa M et al. J Clin Invest. 2009;119:3149-3159.