HUMAN ARTHROPLASTY DERIVED MACROPHAGES DIFFERENTIATE INTO OSTEOCLASTIC BONE-RESORBING CELLS

Objective-In aseptic loosening, a heavy macrophage response to biomate rial wear particles is commonly found in arthroplasty tissues. The aim of this study was to discover if these cells contribute to the bone r esorption of aseptic loosening by differentiating into osteoclasts. Me thods-Macrophages were isolated from the pseudocapsule and pseudomembr ane of loose cemented and uncemented hip arthroplasties at the time of revision surgery and then co-cultured on glass coverslips and dentine slices with UMR 106 rat osteoblast-like cells, both in the presence a nd absence of 1,25 dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. Macrophages isolated from the synovial membrane of patients with osteoarthritis (O A) undergoing hip replacements were similarly studied as a control gro up. Results-After 24 hours incubation, most cells isolated from the ab ove periprosthetic tissues strongly expressed macrophage (CD11b, CD14) but not osteoclast markers. However, after 14 days incubation, numero us multinucleated cells showing the phenotypic features of osteoclasts (that is, positive for tartrate resistant acid phosphatase, the vitro nectin receptor, and capable of extensive lacunar resorption) formed i n co-cultures of arthroplasty derived macrophages and UMR 106 cells, i n the presence of 1,25(OH)(2)D-3. The addition of an antibody to macro phage colony stimulating factor (M-CSF) considerably reduced macrophag e-osteoclast differentiation and hence the lacunar resorption seen in these co-cultures. In contrast, OA synovial macrophage/UMR 106 co-cult ures showed little or no evidence of macrophage-osteoclast differentia tion and this was only seen when human M-CSF was added to the co-cultu res. Conclusion-This is the first report showing that human macrophage s isolated directly from periprosthetic tissues surrounding loosened i mplants differentiate into multinucleated showing all the functional a nd cytochemical characteristics of osteoclasts. In contrast with other macrophage populations, exogenous M-CSF is not required for this to o ccur. In the context of the heavy macrophage response to wear particle s in periprosthetic tissues macrophage-osteoclast differentiation may represent an important cellular mechanism whereby osteolysis is effect ed in aseptic loosening.