Regulation of Bone Cells by Particle-Activated Mononuclear Phagocytes

Bone loss around replacement prostheses may be related to the activation of mononuclear phagocytes (MNP) by prosthetic wear particles. We investigated how osteoblast-like cells were regulated by human MNP stimulated by particles of prosthetic material. Particles of titanium-6-aluminium-4-vanadium (TiAlV) stimulated MNP to release interleukin (IL)-1β, tumour necrosis factor (TNF)α, IL-6 and prostaglandin E 2 (PGE 2 ). All these mediators are implicated in regulating bone metabolism. Particle-activated MNP inhibited bone cell proliferation and stimulated release of IL-6 and PGE 2 . The number of cells expressing alkaline phosphatase, a marker associated with mature osteo-blastic cells, was reduced. Experiments with blocking antibodies showed that TNFα was responsible for the reduction in proliferation and the numbers of cells expressing alkaline phosphatase. By contrast, IL-1β stimulated cell proliferation and differentiation. Both IL-1β and TNFα stimulated IL-6 and PGE 2 release from the osteoblast-like cells. Our results suggest that particle-activated mono-nuclear phagocytes can induce a change in the balance between bone formation and resorption by a number of mechanisms.