Department of Biomedical Research, University of Veterinary Medicine Vienna, Vienna, Austria.
UCB Pharma GmbH, Vienna, Austria.
Sci Rep. 2017 Jul 25;7(1):6460. doi: 10.1038/s41598-017-06614-0.
Estrogen is critical for skeletal homeostasis and regulates bone remodeling, in part, by modulating the expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for bone resorption by osteoclasts. RANKL can be produced by a variety of hematopoietic (e.g. T and B-cell) and mesenchymal (osteoblast lineage, chondrocyte) cell types. The cellular mechanisms by which estrogen acts on bone are still a matter of controversy. By using murine reconstitution models that allow for selective deletion of estrogen receptor-alpha (ERα) or selective inhibition of RANKL in hematopoietic vs. mesenchymal cells, in conjunction with in situ expression profiling in bone cells, we identified bone lining cells as important gatekeepers of estrogen-controlled bone resorption. Our data indicate that the increase in bone resorption observed in states of estrogen deficiency in mice is mainly caused by lack of ERα-mediated suppression of RANKL expression in bone lining cells.
雌激素对于骨骼稳态至关重要，并通过调节核因子-κB 受体激活配体（RANKL）的表达来部分调节骨重塑，RANKL 是破骨细胞进行骨吸收所必需的细胞因子。RANKL 可由多种造血（如 T 和 B 细胞）和间充质（成骨细胞谱系、软骨细胞）细胞类型产生。雌激素作用于骨骼的细胞机制仍存在争议。通过使用允许选择性缺失雌激素受体-α（ERα）或选择性抑制造血细胞与间充质细胞中 RANKL 的小鼠重建模型，结合骨细胞的原位表达谱分析，我们确定了骨衬细胞是雌激素控制的骨吸收的重要守门员。我们的数据表明，在雌激素缺乏的情况下，观察到的骨吸收增加主要是由于骨衬细胞中缺乏 ERα 介导的对 RANKL 表达的抑制。
