PSTPIP2 Limits Osteoclast Precursor Differentiation and Inflammation-Associated Bone Loss.

Abstract 1489

Chronic inflammatory conditions are frequently associated with bone loss. However, the common pathways linking these processes are still poorly defined. Here we show that PSTPIP2, an F-BAR domain containing protein, negatively controls inflammation and osteoclast formation. Mutations in Pstpip2 lead to autoinflammatory disease and secondary generalized osteopenia. Dentine disc implants are more rapidly and extensively resorbed in PSTPIP2-deficient mice than in wt controls due to increased osteoclast formation on the implant. Bone marrow and spleens of cmo mice contain increased numbers of multipotent c-Kit⁺ c-fms^lo Mac-1^lo myeloid precursors that give rise to more osteoclasts in vitro than cells from wt mice. All these phenotypes are corrected by administration of the CCR1 antagonist BX471. Our results identify PSTPIP2 as an essential limiting factor of myelopoiesis and osteoclast differentiation and MIP-1α as a mediator of inflammation-induced bone loss in PSTPIP-2 deficient mice.