人成骨细胞分化及骨保护素分泌:R-脊椎蛋白1通过Wnt/β-catenin通路的作用

Differentiation and osteoprotegerin secretion of human osteoblasts:R-spondin 1 effect via Wnt/beta-catenin signal pathway

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h FOB 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hF OB 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h FOB1.19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。

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,h FOB1.19,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 h FOB1.19 cells.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 h FOB1.19 cells.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.