PLCgamma2: where bone and immune cells find their common ground.

Identifying common signaling pathways to bone and immune system may lead to better therapeutic approaches in diseases such as inflammatory arthritis. In this context, PLCgamma2 seems to be a promising target. PLCgamma2 modulates bone homeostasis by affecting osteoclast recruitment and function. Via its catalytic activity and the adapter domains, PLCgamma2 controls RANKL and alphavbeta3 integrin-dependent signaling pathways in the resorbing cell. Thus, mice lacking PLCgamma2 are osteopetrotic. PLCgamma2 also regulates neutrophil degranulation after beta2 integrin-dependent attachment. Indeed PLCgamma2(-/-) mice are protected from K/BxN serum transfer arthritis, which is known to require neutrophil activation. These studies position PLCgamma2 as a critical regulator of the cellular and molecular mechanisms occurring in bone and immune cells during autoimmune inflammation.