title: ERβ induces the differentiation of cultured osteoblasts by both Wnt/β-catenin signaling pathway and estrogen signaling pathways.
abstract: Although 17β-estradial (E2) is known to stimulate bone formation, the underlying mechanisms are not fully understood. Recent studies have implicated the Wnt/β-catenin pathway as a major signaling cascade in bone biology. The interactions between Wnt/β-catenin signaling pathway and estrogen signaling pathways have been reported in many tissues. In this study, E2 significantly increased the expression of β-catenin by inducing phosphorylations of GSK3β at serine 9. ERβ siRNAs were transfected into MC3T3-E1 cells and revealed that ERβ involved E2-induced osteoblasts proliferation and differentiation via Wnt/β-catenin signaling. The osteoblast differentiation genes (BGP, ALP and OPN) and proliferation related gene (cyclin D1) expression were significantly induced by E2-mediated ERβ. Furthermore immunofluorescence and immunoprecipitation analysis demonstrated that E2 induced the accumulation of β-catenin protein in the nucleus which leads to interaction with T-cell-specific transcription factor/lymphoid enhancer binding factor (TCF/LEF) transcription factors. Taken together, these findings suggest that E2 promotes osteoblastic proliferation and differentiation by inducing proliferation-related and differentiation-related gene expression via ERβ/GSK-3β-dependent Wnt/β-catenin signaling pathway. Our findings provide novel insights into the mechanisms of action of E2 in osteoblastogenesis.
authors.affiliation: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Nephrology, Xi An Honghui Hospital, Xi an, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Xiongke
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, China. Electronic address: zhq9699@126.com.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Zhang
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480020:Atrnl1 protein, mouse; D002272:Carcinoembryonic Antigen; C530105:Ccnd1 protein, mouse; C486183:Ceacam1 protein, mouse; D047629:Estrogen Receptor beta; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D004958:Estradiol; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: 17β-estradial (E2); ERβ; GSK3β; Osteoblast; Wnt/β-catenin signaling; β-catenin