title: Estrogen Receptor α Regulates Dlx3-Mediated Osteoblast Differentiation.
abstract: Estrogen receptor α (ER-α), which is involved in bone metabolism and breast cancer, has been shown to have transcriptional targets. Dlx3 is essential for the skeletal development and plays an important role in osteoblast differentiation. Various osteogenic stimulators and transcription factors can induce the protein expression of Dlx3. However, the regulatory function of ER-α in the Dlx3 mediated osteogenic process remains unknown. Therefore, we investigated the regulation of Dlx3 and found that ER-α is a positive regulator of Dlx3 transcription in BMP2-induced osteoblast differentiation. We also found that ER-α interacts with Dlx3 and increases its transcriptional activity and DNA binding affinity. Furthermore, we demonstrated that the regulation of Dlx3 activity by ER-α is independent of the ligand (estradiol) binding domain. These results indicate that Dlx3 is a novel target of ER-α, and that ER-α regulates the osteoblast differentiation through modulation of Dlx3 expression and/or interaction with Dlx3.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Kyo-Nyeo
authors.initials: KN
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Han
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.
authors.forename: Kwang-Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C088334:Distal-less homeobox proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D018398:Homeodomain Proteins; D008024:Ligands; D014157:Transcription Factors; D004958:Estradiol; D008156:Luciferases
keywords: Dlx3; estrogen receptor α; osteoblast differentiation