Genistein stimulates osteoblastic differentiation via p38 MAPK-Cbfa1 pathway in bone marrow culture  

作　　者：Qing-chuan LIAO Zhou-sheng XIAO Yan-fang QIN Hong-hao ZHOU 

机构地区：[1]Affiliated Children's Hospital, Nanjing Medical University, Nanjing 210008, China [2]Department of Pathology, School of Medicine, Jinan University, Guangzhou 510632, China [3]Institute of Clinical Pharmacology, Central South University, Changsha 410078, China

出　　处：《Acta Pharmacologica Sinica》2007年第10期1597-1602,共6页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China (№30171085);the Teaching and Research Award Program for Outstanding Young Teachers (TRAPOYT № 30040002) in Higher Education Institutions of MOE (Ministry of Education), China.

摘　　要：Aim： To test the hypothesis that genistein stimulates the osteoblastic differentiation through the p38 mitogen activated protein kinase （MAPK）-core-binding factor 1 （Cbfal） pathway. Methods： The activation of p38 MAPK was detected by Western blotting. Alkaline phosphatase （ALP） activity and calcium deposition were assessed for osteoblastic differentiation of bone marrow-derived mesenchymal stem cell （BMSC） cultures. The expression of Cbfal was analyzed at both the mRNA and protein levels. The activity of Cbfal was detected by electrophoretic mobility shift assay. Bone sialoprotein （BSP）, ALP, osteocalcin （OC）, and osteopontin （OPN） gene transcription were also evaluated by either RT-PCR or Northern blotting. Results： Genistein （0.01-1 μmol/L） dose dependently led to the rapid and sustained activation of the p38 MAPK pathway in mouse BMSC cultures. Treatment with genistein （1 μmol/L） resulted in increased ALP activity and calcium deposition of BMSC cultures as a function of time. Genistein also enhanced Cbfal DNA binding activity and promoted the expressions of Cbfal itself as well as several Cbfal-regulated genes, including ALP, BSP, OC, and OPN. Concurrent treatment with p38 MAPK inhibitor （SB203580） diminished the genistein-induced osteoblastic maturation and p38 MAPK-Cbfal activation in mouse BMSC cultures. Conclusion： These results indicated that genistein could stimulate the osteoblastic differentiation of BMSC cultures through the p38 MAPK-Cbfal pathway.Aim： To test the hypothesis that genistein stimulates the osteoblastic differentiation through the p38 mitogen activated protein kinase （MAPK）-core-binding factor 1 （Cbfal） pathway. Methods： The activation of p38 MAPK was detected by Western blotting. Alkaline phosphatase （ALP） activity and calcium deposition were assessed for osteoblastic differentiation of bone marrow-derived mesenchymal stem cell （BMSC） cultures. The expression of Cbfal was analyzed at both the mRNA and protein levels. The activity of Cbfal was detected by electrophoretic mobility shift assay. Bone sialoprotein （BSP）, ALP, osteocalcin （OC）, and osteopontin （OPN） gene transcription were also evaluated by either RT-PCR or Northern blotting. Results： Genistein （0.01-1 μmol/L） dose dependently led to the rapid and sustained activation of the p38 MAPK pathway in mouse BMSC cultures. Treatment with genistein （1 μmol/L） resulted in increased ALP activity and calcium deposition of BMSC cultures as a function of time. Genistein also enhanced Cbfal DNA binding activity and promoted the expressions of Cbfal itself as well as several Cbfal-regulated genes, including ALP, BSP, OC, and OPN. Concurrent treatment with p38 MAPK inhibitor （SB203580） diminished the genistein-induced osteoblastic maturation and p38 MAPK-Cbfal activation in mouse BMSC cultures. Conclusion： These results indicated that genistein could stimulate the osteoblastic differentiation of BMSC cultures through the p38 MAPK-Cbfal pathway.

关 键 词：bone marrow-derived mesenchymal stem cells core-binding factor 1 osteoblastic differentiation GENISTEIN mitogen-activate dprotein kinase 

分 类 号：R5[医药卫生—内科学] R96[医药卫生—临床医学]