Chronic inflammatory diseases of almost any cause are associated with bone loss, and are the consequence of osteoclast induction, differentiation and activation. Tumor necrosis factor-a (TNF-a) is one of the key components of inflammatory. To gain better understanding of the role of TNF-a in osteoclastogenesis, we have investigated direct effects of TNF-a in presence of osteoclast essential factors, M-CSF and RANKL from bone marrow derived macrophages in vitro. We have shown previously that TGF-b is able to inhibit RANKL-induced osteoclast differentiation by a direct action on osteoclast precursors (Lari et al., 2006). The results of this study have indicated that TGF-b also inhibits osteoclast differentiation of either TNF-a or TNF-a and RANKL. Therefore, the data suggests that TGF-b is acting as a direct inhibitor of RANKL-stimulated osteoclast differentiation, in the presence of TNF-a Furthermore, the current study provides some evidence that endogenous type I IFN is contributing substantially to the effects of TNF-a on osteoclast formation in the TNF-a-treated cultures.

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