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Macrophage colony‐stimulating factor and interleukin‐6 release by periprosthetic cells stimulates osteoclast formation and bone resorption
Author(s) -
Neale Susan D.,
Sabokbar Afsaneh,
Howie Donald W.,
Murray David W.,
Athanasou Nicholas A.
Publication year - 1999
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100170510
Subject(s) - osteoclast , vitronectin , macrophage colony stimulating factor , bone resorption , macrophage , tartrate resistant acid phosphatase , medicine , acid phosphatase , microbiology and biotechnology , tumor necrosis factor alpha , interleukin , endocrinology , cytokine , chemistry , biology , immunology , receptor , integrin , biochemistry , in vitro , enzyme
Periprosthetic bone loss is an important contributory factor for aseptic loosening of total joint replacements. It has recently been shown that osteoclast precursor cells are present in the wear particle‐associated macrophage infiltrate found in the membrane surrounding loose implants and that these cells are capable of differentiating into osteoclastic bone‐resorbing cells. Long‐term co‐culture of arthroplasty‐derived macrophages and the rat osteoblast‐like cell line, UMR‐106, in the presence of 1,25 (OH) 2 D 3 results in the formation of numerous multinucleated cells that are positive for tartrate‐resistant acid phosphatase and vitronectin receptor and capable of extensive lacunar bone resorption. The aim of this study was to determine the effect of cytokines/growth factors, known to be present in the arthroplasty membrane, on this process of osteoclast differentiation. During osteoclast formation, increased levels of macrophage colony‐stimulating factor, interleukin‐6, and to a lesser extent, interleukin‐1β, but not tumour necrosis factor α, were detected in the co‐culture supernatants. Addition of neutralising antibodies to human interleukin‐1β or tumour necrosis factor α to the co‐culture system did not inhibit osteoclast formation. In contrast, co‐cultures to which neutralising antibodies to human macrophage colony‐stimulating factor or interleukin‐6 were added contained fewer cells positive for tartrate‐resistant acid phosphatase and vitronectin receptor and formed significantly fewer resorption pits. Time‐course studies showed that macrophage colony‐stimulating factor and interleukin‐6 increase osteoclast formation mainly in the early stages of osteoclast differentiation. These results indicate that the release of macrophage colony‐stimulating factor and interleukin‐6 by activated cells in the arthroplasty membrane is likely to contribute to pathological bone resorption associated with aseptic loosening by stimulating differentiation of mononuclear phagocyte osteoclast precursors into mature bone‐resorbing cells.