骨形态发生蛋白9通过p38激酶途径调控间充质干细胞C3H10T1/2成骨分化  

Bone Morphogenetic Protein 9 Regulate Osteogenic Differentiation of C3H10T1/2 Mesenchymal Stem Cells Through p38 Kinase Pathway

作　　者：赵丹[1,2] 王箭[1] 罗进勇[1] 刘悦亮[1] 王虹[1] 曾照芳[1] 袁军[1,3] 

机构地区：[1]重庆医科大学临床检验诊断学教育部重点实验室,重庆400016 [2]重庆医科大学学生工作处,重庆400016 [3]重庆医科大学科研处,重庆400016

出　　处：《生物化学与生物物理进展》2011年第11期1001-1010,共10页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(30800658;31071304);重庆市科委自然科学基金(2009BB5060)资助项目~~

摘　　要：前期研究发现骨形态发生蛋白9(bone morphogenetic protein 9,BMP9)具有较强的诱导间充质干细胞成骨分化的能力.为进一步揭示其诱导和调控间充质干细胞成骨分化的机理,利用BMP9重组腺病毒感染间充质干细胞C3H10T1/2,通过体外细胞实验和体内动物实验,初步分析BMP9是否可通过p38激酶途径调控间充质干细胞成骨分化.结果发现,BMP9可以通过促进p38激酶磷酸化而导致其活化,p38抑制剂SB203580可抑制由BMP9诱导的C3H10T1/2细胞的碱性磷酸酶(alkalinephosphatase,ALP)活性、骨桥蛋白(osteopontin,OPN)表达和钙盐沉积,而且利用抑制剂SB203580抑制p38激酶活性后,BMP9诱导的Smad经典途径的激活也相应受到抑制,RNA干扰导致p38基因沉默同样也可抑制BMP9诱导的ALP活性、OPN表达、钙盐沉积以及裸鼠皮下异位成骨.因此,BMP9可通过活化p38激酶途径调控间充质干细胞C3H10T1/2成骨分化.In the previous reports,bone morphogenetic protein 9（BMP9） has shown potent function to induce osteogenic differentiation of mesenchymal stem cells,however,the underlying molecular mechanism of osteogenesis induced by BMP9 is needed to be deep explored.BMP9 was introduced into C3H10T1/2 mesenchymal stem cells by recombinant adenoviruses protocol,then,in vitro and in vivo assays were conducted to evidence whether BMP9 can induce osteogenic differentiation of C3H10T1/2 mesenchymal stem cells through p38 kinase pathway.The results showed that BMP9 can activate p38 kinase through increasing the phosphorylated form of p38 kinase.P38 kinase inhibitor SB203580 can inhibit the ALP activity,OPN expression and calcium deposition of C3H10T1/2 cells induced by BMP9.Furthermore,SB203580 also led to inhibition of canonical Smad pathway activated by BMP9.Moreover,when p38 kinase was silenced by RNA interference in C3H10T1/2 cells,BMP9-induced ALP activity,OPN expression,calcium deposition and in invo ectopic bone formation were accordingly inhibited along with knockdown of p38 kinase.Taken together,those results intensively suggested that BMP9 can induce and regulate osteogenic differentiation of mesenchymal stem cells through activating p38 kinase pathway.

关 键 词：骨形态发生蛋白9 P38 间充质干细胞 成骨分化 丝裂原活化蛋白激酶 

分 类 号：Q257[生物学—细胞生物学] R341[医药卫生—基础医学]