Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis.

Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generated osteoblast-specific -deficient () mice using 2.3-kb Cre. Trabecular bone volume and the trabecular number were lower in mice of both sexes than in mice. In bone histomorphometric analysis, osteoclast parameters were increased in mice, whereas osteoblast parameters and the bone formation rate were similar to those in mice. TUNEL-positive osteoblastic cells and serum TRAP5b levels were increased in mice. The deletion of in osteoblasts induced expression, whereas the overexpression of had no effect. In a co-culture of -deficient primary osteoblasts and wild-type bone-marrow-derived monocyte/macrophage lineage cells, the numbers of multinucleated TRAP-positive cells and resorption pits increased. Furthermore, serum deprivation or the deletion of in primary osteoblasts increased apoptosis and ATP levels in the medium. Therefore, the reduction in trabecular bone in mice may be due to enhanced bone resorption through osteoblast apoptosis and the release of ATP from apoptotic osteoblasts, and may inhibit bone resorption by preventing osteoblast apoptosis.