Aseptic Loosening Osteoclast Osteoblast Macrophage HUMAN OSTEOBLASTIC CELLS SUPPORT OSTEOCLAST FORMATION FROM ARTHROPLASTY-DERIVED MACROPHAGES

Introduction: A predominant histological feature of periprosthetic tissue surrounding aseptically loose implant components is the presence of a prominent foreign body macrophage response to prosthesis derived wear. A number of potent bone resorbing mediators have been identified in periprosthetic tissue from around loose prostheses and these mediators have been shown to be released from wear particle stimulated macrophages both in vivo and in vitro. However, the cellular mechanisms underlying aseptic loosening of implant components and the manner in which this foreign body macrophage infiltrate in periprosthetic tissues contributes to osteolysis remain uncertain. Recent studies have shown that murine monocytes and inflammatory macrophages responding to prosthesis wear particles are capable of differentiating into osteoclastic bone resorbing cells. Thus, one cellular mechanism whereby bone resorption and implant loosening may occur is by osteoclastic differentiation of precursor cells present in periprosthetic tissue. Recently it was reported that macrophages isolated from the pseudomembrane surrounding failed joint arthroplasties, when co-cultured with rat osteoblast-like cells, UMR106, in the presence of 1,25(OH)2D3, were capable of differentiating into osteoclastic bone resorbing cells. In order to develop an in vitro system of human macrophage-osteoclast differentiation which more closely parallels what occurs in vivo, we sought to determine if human bone derived stromal cells were capable of supporting the differentiation of arthroplasty-derived macrophages into osteoclastic bone resorbing cells.