title: Purification and identification of estrogen receptor alpha co-regulators in osteoclasts.
abstract: Mature osteoclasts are multinuclear, macrophage-like cells derived from hematopoietic stem cells in the bone marrow. Several transcription factors regulating osteoclast differentiation have been identified. However, the molecular basis of transcriptional regulation in osteoclasts at epigenetic levels is largely unknown. In fact, no osteoclast-specific transcriptional co-regulators have been characterized. Recently, selective ablation of estrogen receptor alpha (ERalpha) in mature osteoclasts derived from female mice (ERalpha(Deltaoc/Deltaoc)) exhibited trabecular bone loss due to induced apoptosis via upregulated expression of Fas ligand mRNA. In general, the component composition of the ERalpha-associated co-activator complex and its expression levels are distinct among tissues. However, ERalpha transcriptional co-regulators in mature osteoclasts remain unclear. In the present study, we achieved large-scale cultivation of mature, multinucleated osteoclasts and established a purification system for ERalpha-associated proteins. In addition to co-regulators previously found in other ERalpha target cells, several unexpected factors were found such as CAP-H. The mRNA expression level of CAP-H was high during osteoclast differentiation. These results demonstrate the existence of osteoclast-specific transcriptional co-regulators supporting ERalpha function.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.forename: Naoya
authors.initials: N
authors.lastname: Tsuji
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Youn
authors.forename: Sally
authors.initials: S
authors.lastname: Fujiyama
authors.forename: Maiko
authors.initials: M
authors.lastname: Okada
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Shino
authors.initials: S
authors.lastname: Kondo
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitakawa
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasuda
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D056970:Co-Repressor Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010010:Osteoclasts / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D015534:Trans-Activators