Purification and identification of estrogen receptor alpha co-regulators in osteoclasts.
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.
Takada
Ichiro
I
Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan.
Tsuji
Naoya
N
Youn
Min-Young
MY
Fujiyama
Sally
S
Okada
Maiko
M
Imai
Yuuki
Y
Kondo
Shino
S
Kitakawa
Hirochika
H
Yasuda
Hisataka
H
Kato
Shigeaki
S
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
D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D015534:Trans-Activators