Estrogen receptor α in mature osteoblasts regulates the late stage of bone regeneration
Estrogen receptor α in mature osteoblasts regulates the late stage of bone regeneration
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DOI：
10.1016/j.bbrc.2021.04.112
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发表时间：
2021-05-05
影响因子：
3.1
通讯作者：
Imai, Yuuki
中科院分区：
文献类型：
--
作者：
Ikedo, Aoi;Imai, Yuuki
雌激素缺乏会损害骨折愈合和骨组织的稳态。ovx诱导的小鼠雌激素缺乏可减缓骨折愈合，改变骨折愈合过程中骨痂中雌激素受体(ER) α和ER β的表达比例。因此，er可能参与了骨折愈合的调控。然而，内质网在骨折愈合中的作用在很大程度上是未知的。本研究的目的是利用成骨细胞特异性内质网敲除小鼠在单皮质钻孔骨再生模型中阐明内质网在骨折愈合中的意义。利用骨钙素(OCN)-Cre小鼠、ER α和ER β flox小鼠(OCN-Cre; ER α (f/f)、ER α (δ Ob/ δ Ob)和OCN-Cre，制备成熟成骨细胞特异性ER敲除小鼠；ER （f/f) ER (Ob/ Ob)）对8周龄雌性小鼠胫骨进行钻孔手术。术后10、14 d处死小鼠，采用DXA、mu CT和骨组织形态学分析。DXA分析显示，与ER α (f/f)小鼠相比，ER α (δ Ob/ δ Ob)小鼠的完整股骨骨密度显著降低，但ER β (δ Ob/ δ Ob)和ER β (f/f)小鼠的骨量没有差异。显微CT分析显示，仅在第14天，小鼠胫骨受限钻孔部位的ER α (δ Ob/ δ Ob)与ER α (f/f)相比，ER α (δ Ob/ δ Ob)的愈伤组织体积明显减少，而在第10天则没有。除股骨骨密度外，ER β (δ Ob/ δ Ob)和ER β (f/f)小鼠之间的愈伤组织体积无显著差异。骨组织形态学分析显示Ob.S/BS和N.Ob/B。仅在第10天，与ER α (f/f)小鼠相比，ER α (δ Ob/ δ Ob)小鼠的Pm明显减少。此外，Oc。S/BS和N.Oc/B。仅在第14天，与ER α (f/f)小鼠相比，ER α (δ Ob/ δ Ob)小鼠的Pm明显减少。这些结果表明，在骨钙素阳性的成骨细胞中，ER α而不是ER β可能有助于后期骨再生。(C) 2021爱思唯尔公司版权所有。
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 ER beta 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 ER alpha and ER beta flox mice (OCN-Cre; ER alpha(f/f), ER alpha(Delta Ob/Delta Ob) and OCN-Cre; ER beta(f/f), ER beta(Delta Ob/Delta Ob)). 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, mu CT and bone histomorphometry.DXA analysis revealed that intact femoral BMD was significantly decreased in ER alpha(Delta Ob/Delta Ob) mice compared with ER alpha(f/f) mice, but there was no difference in bone mass between ER beta(Delta Ob/Delta Ob) and ER beta(f/f) mice. Micro CT analyses showed that the callus volume at the restricted drill hole site in tibiae was significantly less in ER alpha(Delta Ob/Delta Ob) compared to ER alpha(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 ER beta(Delta Ob/Delta Ob) and ER beta(f/f) mice. Bone histomorphometric analyses showed that Ob.S/BS and N.Ob/B.Pm were significantly less in ER alpha(Delta Ob/Delta Ob) mice compared with ER alpha(f/f) mice only at day 10. In addition, Oc.S/BS and N.Oc/B.Pm were significantly less in ER alpha(Delta Ob/Delta Ob) mice compared with ER alpha(f/f) mice only at day 14.These results suggest that ER alpha but not ER beta in osteocalcin-positive osteoblasts may contribute to the late stage of bone regeneration. (C) 2021 Elsevier Inc. All rights reserved.