Involvement of interleukin 1 and tumour necrosis factor alpha as endogenous growth factors in human osteoblastic...

Normal human osteoblastic (OB) cells produce several haematopoietic factors, including IL-1, IL-6, PGE2 and TNF-alpha. However, it is unknown whether these factors play a role as autocrine mitogenic factors. We show here that some of these cytokines released by OB cells are endogenous growth factors for OB cells. Conditioned medium (CM) obtained from quiescent OB cells, dose-dependently stimulated OB cell proliferation, suggesting the production of autocrine growth factors by OB cells. Treatment with exogenous rhIL-1 and rhTNF-alpha increased OB cell growth. We found that neutralizing antibodies against IL-1 and TNF-alpha at concentrations that specifically inhibited the mitogenic activity of these cytokines, suppressed part of the mitogenic effect of CM on quiescent OB cells cultured at low or high density. In contrast, treatment of OB cells with indomethacin at a dose (10(-6) M) that inhibits endogenous prostaglandin production, increased OB cell proliferation in the presence or absence of CM, indicating that the mitogenic effect of CM on OB cells was not due to PGE2. In addition, exogenous recombinant human (rh)IL-6, or a specific neutralizing anti-IL-6 antibody, did not affect the OB cell proliferation. The results indicate that, in contrast to PGE2 and IL-6, IL-1 and TNF-alpha released by OB cells act as endogenous mitogenic factors for human osteoblasts.