BACKGROUND:Studies have funded that reduced Wnt/β-catenin signaling is involved in the onset and/or progression of bone erosion in rheumatoid arthritis. It can lead to potential new treatment approaches of bone erosion by enhancing Wnt/β-catenin signaling pathway. R-spondin 1 may act as a Wnt agonist, but there is no study in human osteoblasts. OBJECTIVE:To verify the effect of R-spondin 1 on promoting differentiation and maturation of human osteoblasts by inhibiting DKK1. METHODS:S40-transfected human osteoblast lines, hFOB1.19, were treated with R-spondin 1, Wnt-3a and DKK1 to detecting the proliferation, alkaline phoshpatase activity and osteoprotegerin concentration. RESULTS AND CONCLUSION:R-spondin 1 had no effects on hFOB1.19 cel s. Wnt-3a upregulated the activity of alkaline phoshpatase, which could be enhanced by addition of R-spondin 1. R-spondin 1 could reduce the DKK1-mediated inhibition of alkaline phoshpatase activity in hFOB1.19 cel s. R-spondin 1 increased the concentration of osteoprotegerin, and moreover, the promotion of osteoprotegerin by R-spondin 1 alone was stronger than the inhibition by DKK1. These findings suggest that R-spondin 1 can inhibit DKK1 by Wnt/β-catenin signal pathway to promote the differential and maturation of human osteoblasts to excrete osteoprotegerin.%背景：研究表明Wnt/β-catenin信号通路活性受抑是类风湿关节炎骨侵蚀的始动因素，增强该通路有望治疗类风湿关节炎关节破坏。R-脊椎蛋白1(RSpo1)可能是Wnt激活剂，尚无人成骨细胞相关研究。 目的：验证R-脊椎蛋白1抑制DKK1促进该细胞的分化成熟。 方法：给予S40转染人成骨细胞株hFOB 1.19 Wnt-3a、R-脊椎蛋白1及Wnt信号通路抑制剂DKK1不同刺激，通过检测细胞增殖、碱性磷酸酶活性及骨保护素水平，观察R-脊椎蛋白1在成骨细胞中的作用。 结果与结论：R-脊椎蛋白1对hFOB 1.19细胞增殖无影响，Wnt-3a上调碱性磷酸酶活性，与R-脊椎蛋白1共刺激可增强该作用；R-脊椎蛋白1可减少DKK1对hFOB1.19细胞碱性磷酸酶活力的抑制作用。R-脊椎蛋白1可提高骨保护素质量浓度，但R-脊椎蛋白1对骨保护素的增强作用大于DKK1对其的抑制作用。提示R-脊椎蛋白1通过抑制DKK1，参与Wnt/β-catenin信号通路，促进成骨细胞分化成熟，分泌骨保护素。
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