Introductions:Tumor necrosis factor- (TNF-) is one of the key components of inflammatory. It plays a crucial role in the bone and joint destruction that occurs in chronic inflammation. Methods:To gain better understanding of the role of TNF- in osteoclastogenesis, we have investigated direct effects of TNF- on osteoclast differentiation by M-CSF and RANKL from bone marrow derived macrophages in vitro. Results and Conclusions: Although, at low concentrations, TNF- acted as a co stimulator with RANKL, at high concentration (10 ng/ml) it significantly suppressed the proliferation of osteoclast precursors (p <0.01). In high concentration it significantly down regulated the RANKL-induced osteoclastic genes expression, CTR and Cath K, as measured by Q-PCR (p< 0.05). Also in this study it has been shown that endogenous type I IFN is contributing substantially to the effects of TNF-on osteoclast formation. Taken together, the above results from this study give a better insight into the complex mechanisms of how TNF- may be linked to osteoclastogenesis in inflammatory conditions.

Keywords