FGFR1在雌激素调控成骨细胞增殖分化过程中的作用研究  

Study on the role of FGFR1 in the process of proliferation and differentiation of osteoblasts regulated by estrogen

作　　者：魏霆 肖国宁 孙惠强[1] WEI Ting;XIAO Guo-ning;SUN Hui-qiang(Dept. o f Prosthodontics, College of Stomatology, Shandong University, Shandong 250012, China)

机构地区：[1]山东大学口腔医学院修复科,山东250012 [2]天津医科大学总医院,天津300052

出　　处：《口腔颌面修复学杂志》2018年第2期113-118,共6页Chinese Journal of Prosthodontics

基　　金：山东省自然科学基金(项目编号:2014ZRE27342)

摘　　要：目的:明确Ⅰ型成纤维细胞生长因子受体(FGFR1)在雌激素促成骨细胞增殖分化过程中的作用,并进一步探索其作用机制。方法:在雌激素作用下采用抑制剂PD166866抑制FGFR1的活性,(四唑甲基噻唑)MTT、(碱性磷酸酶)ALP检测成骨细胞增殖分化活性;Western blot比较各组成骨细胞Runx2和OCN表达水平以及(丝裂原活化蛋白激酶)MAPK信号通路关键因子ERK1/2,JNK,P38表达水平及磷酸化水平。结果:雌激素作用下,加入抑制剂后,成骨细胞中MTT值明显降低,ALP值明显增高(P<0.05),且Runx2,OCN蛋白表达水平明显增高(P<0.05);雌激素作用下,ERK、JNK和P38蛋白表达无明显改变,但磷酸化水平均显著升高,加入抑制剂后,仅ERK磷酸化水平明显上升(P<0.05)。结论:本实验结果提示FGFR1对成骨细胞具有促进增殖、抑制分化的作用,且介导雌激素调控成骨细胞增殖分化的过程;此外,多条MAPK信号通路中,仅ERK通路参与了该过程。Objective： To investigate the role of fibroblast growth factor receptor 1 （FGFR1） in the proliferation and dif-ferentiation of bone cells induced by estrogen, and to further explore the FGFR1 regulatory mechanism on MC3T3-E1 cells. Methods： Under the action of estrogen, inhibitor PD166866 was used to inhibit the activity of FGFR1. Methyl thiazol tetra- zolium （MTT） and alkaline phosphatase （ALP） were used to detect the proliferation and differentiation acivties of os-teoblasts. The expression levels of Runx2 and OCN of osteoblasts in each group, and the expression levels and phosphory-lation levels of the key genes（ERK1/2 , JNK, P38） in the MAPK signaling pathway by Western blot were compared and ele-vated. Results： Under the effects of estrogen, treatment with inhibitor PD166866 reduced the MTT values, increased ALP activity and increased the levels of Runx2 and OCN protein significantly （P 〈0.05）. And under the effects of estrogen, no significant changes on the expression level of ERK, JNK and P38 while the phosphorylation levels of ERK, JNK and P38 is higher （P〈0.05）. After adding the FGFR1 inhibitor PD166866, only the phosphorylation level of ERK increased （P〈0.05）. Conclusion： FGFR1 may promote osteoblast proliferation and inhibit osteoblast differentiation, and participate in the pro-cess of estrogen regulating osteoblast proliferation and differentiation. And in multiple MAPK signaling pathways, only the ERK pathway participates in the process.

关 键 词：雌激素 I型成纤维细胞因子受体 成骨细胞 ERK/MAPK信号通路 

分 类 号：R780.2[医药卫生—口腔医学]