ONCOSTATIN-M STIMULATES MACROPHAGE-POLYKARYON FORMATION IN LONG-TERM HUMAN BONE-MARROW CULTURES

Though oncostatin M (OSM) is a potent mediator of the inflammatory rea ction, its role in inflammation and bone resorption is still unclear, A long-term bone-marrow culture system is usually developed to allow t he formation of multinucleated cells (MNC) and was used here to define the effects of human recombinant OSM on human MNC formation, OSM sign ificantly upregulated (1.9- to 5.6-fold) the number of MNC in these cu ltures in a dose-and time-dependent manner, Cell nucleation and tartra te-resistant acid phosphatase activity were also increased, MNC did no t display osteoclast characteristics, such as response to calcitonin a nd failure to resorb dentin surface, However, they expressed a non-spe cific ar-naphthyl acetate esterase as well as macrophage differentiati on antigens (CD11b, CD13 and CD33) and were able to perform phagocytos is, Similar effects were observed after addition of 1 alpha,25-dihydro xyvitamin D3, Moreover, in these culture conditions, human bone-marrow mononuclear cells were capable of low-grade resorption in the presenc e of bone-marrow stromal cells, This low-grade resorption was signific antly inhibited by addition of 25 ng/ml OSM, Our data demonstrate for the first time that human recombinant OSM significantly stimulates the formation of MNC and could be involved in the inflammatory process vi a macrophage-polykaryon formation from human bone marrow. (C) 1998 Aca demic Press Limited.