The interaction of the macrophage and the osteoblast in the pathophysiology of aseptic loosening of joint replacements.
Macrophage phagocytosis of cement particles with production of inflammatory mediators is a component of the underlying mechanism of aseptic loosening of joint prostheses. Prostaglandin E2 (PGE2), a bone resorbing mediator, has been implicated in the loosening process. Investigations have shown that macrophage phagocytosis of cement particles leads to production of bone-resorbing mediators other than PGE2. In this study, conditioned medium from macrophages exposed to crushed simplex cement particles stimulated osteoblasts to release radiolabeled arachidonic acid and metabolites. Incubation of osteoblasts in conditioned medium from macrophages exposed to cement particles small enough to be phagocytized increased PGE2 release 80-fold over unexposed osteoblasts (P < 0.001). Incubation of osteoblasts in conditioned medium from macrophages exposed to particles too large to be phagocytized, or to bone cement filtrate, did not stimulate PGE2 release. We propose that the role of the macrophage in aseptic loosening is primarily to recognize the mechanical failure of the cement mantle by phagocytosis of cement particles and subsequent production of small amounts of specific mediators. These mediators stimulate surrounding osteoblasts to secrete PGE2, which then amplifies the inflammatory response and ultimately results in bone resorption and aseptic loosening.
Horowitz
S M
SM
Hospital For Special Surgery, New York, New York.
Rapuano
B P
BP
Lane
J M
JM
Burstein
A H
AH
D016718:Arachidonic Acid / Q000378:metabolism; D001843:Bone Cements / Q000378:metabolism; D002460:Cell Line; D017077:Culture Media, Conditioned; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007595:Joint Prosthesis; D008264:Macrophages / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology*; D010587:Phagocytosis; D011475:Prosthesis Failure
D001843:Bone Cements; D017077:Culture Media, Conditioned; D016718:Arachidonic Acid; D015232:Dinoprostone