Feng Xiaoke, Lv Chengyin, Wang Fang, Gan Ke, Zhang Miaojia, Tan Wenfeng
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China ; Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
Clin Dev Immunol. 2013;2013:160123. doi: 10.1155/2013/160123. Epub 2013 Nov 18.
Receptor activator of nuclear factor κ B ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis. Considering that 1,25(OH)2D3 has been suggested as a potent inducer of RANKL expression, it should clarify whether vitamin D supplement could result in RANKL overexpression and thereby facilitate excessive osteoclastogenesis and bone resorption in RA. Here, we investigated modulatory effect of 1,25(OH)2D3 on the expression of RANKL and its decoy receptor osteoprotegerin (OPG) in an inflammatory condition of human rheumatoid synoviocyte MH7A. MH7A cells were stimulated with IL1 β and then treated with different concentrations of 1,25(OH)2D3 for 48 h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNF β mRNA expression in cells and IL-6 protein in supernatants were observed in IL1 β -induced MH7A in the presence of 1,25(OH)2D3 compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both 1,25(OH)2D3 and IL1 β . In summary, although it has a biological function to induce RANKL expression, 1,25(OH)2D3 could upregulate OPG/RANKL ratio and mediate anti-inflammatory action in an inflammatory milieu of synoviocyte, contributing to the inhibition of inflammation-induced osteoclastogenesis in RA.
核因子κB受体活化因子配体（RANKL）通过促进破骨细胞生成，在类风湿关节炎（RA）的骨侵蚀中起关键作用。鉴于1,25(OH)₂D₃被认为是RANKL表达的有效诱导剂，应明确补充维生素D是否会导致RANKL过表达，从而促进RA中过度的破骨细胞生成和骨吸收。在此，我们研究了1,25(OH)₂D₃在人类风湿滑膜细胞MH7A炎症状态下对RANKL及其诱饵受体骨保护素（OPG）表达的调节作用。用IL-1β刺激MH7A细胞，然后用不同浓度的1,25(OH)₂D₃处理48小时。与未添加1,25(OH)₂D₃相比，在1,25(OH)₂D₃存在的情况下，IL-1β诱导的MH7A细胞中OPG/RANKL比值显著升高，细胞中IL-6和TNF-β mRNA表达水平以及上清液中IL-6蛋白水平明显降低。当RAW264.7细胞同时用1,25(OH)₂D₃和IL-1β处理时，破骨细胞形成明显减少。总之，尽管1,25(OH)₂D₃具有诱导RANKL表达的生物学功能，但它可以上调OPG/RANKL比值，并在滑膜细胞炎症环境中介导抗炎作用，有助于抑制RA中炎症诱导的破骨细胞生成。
