POLYMETHYLMETHACRYLATE-STIMULATED MACROPHAGES INCREASE RAT OSTEOCLASTPRECURSOR RECRUITMENT THROUGH THEIR EFFECT ON OSTEOBLASTS IN-VITRO

An in vitro rat osteoclast precursor model was employed to study the r ole of macrophages in the osteolysis associated with aseptic loosening of cemented total joint replacements. Bone resorption at the bone-bon e cement interface may involve the release of mediators by macrophages in response to phagocytosis of polymethylmethacrylate particles. Two potential pathways for the macrophage-directed bone resorption were st udied. An indirect pathway was investigated in which the macrophage re sponse to cement particles was used to stimulate rat osteosarcoma (ROS ) 17/2.8 osteoblasts. Osteoblast-soluble factors then were added to os teoclast precursors. In the direct pathway, osteoclast precursors were exposed directly to macrophage-soluble factors released in response t o phagocytosis of cement particles. Osteoclast precursors were identif ied after adherence to polished human dentin slices. Acid phosphatase- positive osteoclasts were counted using light microscopy at x200 magni fication. In the indirect pathway, where the macrophage response was m ediated through the rat osteosarcoma osteoblasts. a significant increa se in the recruitment of osteoclast precursors was observed. In the di rect pathway when the macrophage-conditioned medium was allowed to int eract directly with osteoclast precursors, the adherence of the precur sors was significantly decreased. This demonstrates that the macrophag e mediators released following phagocytosis of polymethylmethacrylate particles affect the release of soluble factors from osteoblasts. In t urn, these osteoblast factors stimulate recruitment of osteoclast prec ursors to calcified tissue. Evidence from this in vitro model reveals that macrophage-soluble factors, in the absence of an osteoblast contr ibution, decrease the adherence of osteoclast precursors to calcified substrate. We propose that bone resorption at the aseptically loose in terface of cemented arthroplasty may be mediated, at least in part, by soluble factors secreted by osteoblasts responding to macrophages tha t have phagocytosed particles of polymethylmethacrylate cement.