Phospholipase C gamma 2 is required for basal but not oestrogen deficiency-induced bone resorption

Background Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase C gamma 2 (PLC gamma 2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLC gamma 2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLC gamma 2-deficient (PLC gamma 2-/-) mice. Materials and methods The trabecular architecture of long bone metaphyses was tested by micro-CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLC gamma 2 phosphorylation were tested on in vitro osteoclast and macrophage cultures. Results PLC gamma 2-/- mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLC gamma 2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLC gamma 2 was phosphorylated in a Src-family-dependent manner upon macrophage adhesion but not upon stimulation by M-CSF or RANKL. Surprisingly, ovariectomy-induced bone resorption in PLC gamma 2-/- mice was similar to, or even more robust than, that in wild-type animals. Conclusions Our results indicate that PLC gamma 2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLC gamma 2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiencyinduced bone resorption utilizes different signalling pathways and that PLC gamma 2 may not be a suitable therapeutic target in postmenopausal osteoporosis.