Polymethylmethacrylate-stimulated macrophages increase rat osteoclast precursor recruitment through their effect on osteoblastsin vitro

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Abstract
An in vitro rat osteoclast precursor model was employed to study the role of macrophages in the osteolysis associated with aseptic loosening of cemented total joint replacements. Bone resorption at the bone‐bone 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 studied. An indirect pathway was investigated in which the macrophage response to cement particles was used to stimulate rat osteosarcoma (ROS) 17/2.8 osteoblasts. Osteoblast‐soluble factors then were added to osteoclast precursors. In the direct pathway, osteoclast precursors were exposed directly to macrophage‐soluble factors released in response to phagocytosis of cement particles. Osteoclast precursors were identified after adherence to polished human dentin slices. Acid phosphatase‐positive osteoclasts were counted using light microscopy at ×200 magnification. In the indirect pathway, where the macrophage response was mediated through the rat osteosarcoma osteoblasts, a significant increase in the recruitment of osteoclast precursors was observed. In the direct pathway, when the macrophage‐conditioned medium was allowed to interact directly with osteoclast precursors, the adherence of the precursors was significantly decreased. This demonstrates that the macrophage mediators released following phagocytosis of polymethylmethacrylate particles affect the release of soluble factors from osteoblasts. In turn, these osteoblast factors stimulate recruitment of osteoclast precursors to calcified tissue. Evidence from this in vitro model reveals that macrophage‐soluble factors, in the absence of an osteoblast contribution, decrease the adherence of osteoclast precursors to calcified substrate. We propose that bone resorption at the aseptically loose interface of cemented arthroplasty may be mediated, at least in part, by soluble factors secreted by osteoblasts responding to macrophages that have phagocytosed particles of polymethylmethacrylate cement.

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