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Publication : Estrogen receptor α in mature osteoblasts regulates the late stage of bone regeneration.

First Author  Ikedo A Year  2021
Journal  Biochem Biophys Res Commun Volume  559
Pages  238-244 PubMed ID  33964733
Mgi Jnum  J:305938 Mgi Id  MGI:6705946
Doi  10.1016/j.bbrc.2021.04.112 Citation  Ikedo A, et al. (2021) Estrogen receptor alpha in mature osteoblasts regulates the late stage of bone regeneration. Biochem Biophys Res Commun 559:238-244
abstractText  Estrogen deficiency impairs fracture healing and homeostasis of bone tissue. OVX-induced estrogen deficiency in mice attenuates fracture healing and changes the expression ratio of estrogen receptor (ER) alpha and ERbeta in callus during the process of fracture healing. Therefore, ERs may be involved in the regulation of fracture healing. However, the roles of ERs in fracture healing are largely unknown. The purpose of this study was to clarify the significance of ERs during fracture healing using osteoblast-specific ER knockout mice in a mono-cortical drill hole bone regeneration model. The mature osteoblast-specific ER knockout mice were generated using osteocalcin (OCN)-Cre mice, and ERalpha and ERbeta flox mice (OCN-Cre; ERalpha(f/f), ERalpha(DeltaOb/DeltaOb) and OCN-Cre; ERbeta(f/f), ERbeta(DeltaOb/DeltaOb)). Drill hole surgery was conducted on the tibiae of 8-week-old female mice. The mice were sacrificed 10 or 14 days after surgery and the bones were analyzed by DXA, muCT and bone histomorphometry. DXA analysis revealed that intact femoral BMD was significantly decreased in ERalpha(DeltaOb/DeltaOb) mice compared with ERalpha(f/f) mice, but there was no difference in bone mass between ERbeta(DeltaOb/DeltaOb) and ERbeta(f/f) mice. Micro CT analyses showed that the callus volume at the restricted drill hole site in tibiae was significantly less in ERalpha(DeltaOb/DeltaOb) compared to ERalpha(f/f) mice only at day 14 but not at day 10. In addition to femoral BMD, there was no significant difference in callus volume between ERbeta(DeltaOb/DeltaOb) and ERbeta(f/f) mice. Bone histomorphometric analyses showed that Ob.S/BS and N.Ob/B.Pm were significantly less in ERalpha(DeltaOb/DeltaOb) mice compared with ERalpha(f/f) mice only at day 10. In addition, Oc.S/BS and N.Oc/B.Pm were significantly less in ERalpha(DeltaOb/DeltaOb) mice compared with ERalpha(f/f) mice only at day 14. These results suggest that ERalpha but not ERbeta in osteocalcin-positive osteoblasts may contribute to the late stage of bone regeneration.
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