Abstract
Osteoprotegerin (OPG) is a recently cloned soluble member of the tumor necrosis factor receptor family. OPG has been shown to inhibit osteoclast recruitment by binding to OPG-ligand, an osteoclast differentiating factor on osteoblastic stromal cells, thereby blocking osteoclastogenesis. In this report we have examined the effect of tumor necrosis factor-α (TNF-α) and tumor necrosis factor-β (TNF-β) on OPG mRNA levels in the human osteosarcoma cell line MG-63. We demonstrate that both TNF-α and TNF-β dose- and time-dependently upregulate the mRNA levels of OPG. The effect is significant at and above 5 pM of TNF-α and 1 pM of TNF-β. The stimulatory effect on OPG mRNA levels in MG-63 cells was detected after 2 hrs of incubation with TNF-α or TNF-β. These data demonstrate that the expression of OPG in osteoblasts, with subsequent effects on osteoclastogenesis, is regulated by TNFs.
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