Brändström H, Jonsson K B, Vidal O, Ljunghall S, Ohlsson C, Ljunggren O
Department of Medical Sciences, University of Uppsala, Sweden.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):454-7. doi: 10.1006/bbrc.1998.8993.
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-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on OPG mRNA levels in the human osteosarcoma cell line MG-63. We demonstrate that both TNF-alpha and TNF-beta dose- and time-dependently upregulate the mRNA levels of OPG. The effect is significant at and above 5 pM of TNF-alpha and 1 pM of TNF-beta. The stimulatory effect on OPG mRNA levels in MG-63 cells was detected after 2 hrs of incubation with TNF-alpha or TNF-beta. These data demonstrate that the expression of OPG in osteoblasts, with subsequent effects on osteoclastogenesis, is regulated by TNFs.
骨保护素（OPG）是肿瘤坏死因子受体家族中最近克隆出的可溶性成员。研究表明，OPG通过与OPG配体结合来抑制破骨细胞募集，OPG配体是一种存在于成骨细胞基质细胞上的破骨细胞分化因子，从而阻断破骨细胞生成。在本报告中，我们研究了肿瘤坏死因子-α（TNF-α）和肿瘤坏死因子-β（TNF-β）对人骨肉瘤细胞系MG-63中OPG mRNA水平的影响。我们证明，TNF-α和TNF-β均以剂量和时间依赖性方式上调OPG的mRNA水平。当TNF-α浓度达到及高于5 pM以及TNF-β浓度达到及高于1 pM时，这种影响具有显著性。在用TNF-α或TNF-β孵育2小时后，检测到对MG-63细胞中OPG mRNA水平的刺激作用。这些数据表明，成骨细胞中OPG的表达及其对破骨细胞生成的后续影响受TNFs调控。
