Research Center CHU Sainte-Justine, 3175 Chemin de la Cote-Sainte-Catherine, Montréal, QC H3T 1C5, Canada.
Department of Basic Biomedical Sciences, Sanford Medical School, University of South Dakota, Vermillion, SD 57069, USA.
Genes (Basel). 2023 May 19;14(5):1111. doi: 10.3390/genes14051111.
Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity. The incidence of AIS in females is 8.4 times higher than in males. Several hypotheses on the role of estrogen have been postulated for the progression of AIS. Recently, Centriolar protein gene POC5 () was identified as a causative gene of AIS. POC5 is a centriolar protein that is important for cell cycle progression and centriole elongation. However, the hormonal regulation of POC5 remains to be determined. Here, we identify as an estrogen-responsive gene under the regulation of estrogen receptor ERα in normal osteoblasts (NOBs) and other ERα-positive cells. Using promoter activity, gene, and protein expression assays, we found that the gene was upregulated by the treatment of osteoblasts with estradiol (E2) through direct genomic signaling. We observed different effects of E2 in NOBs and mutant AIS osteoblasts. Using promoter assays, we identified an estrogen response element (ERE) in the proximal promoter of , which conferred estrogen responsiveness through ERα. The recruitment of ERα to the ERE of the promoter was also potentiated by estrogen. Collectively, these findings suggest that estrogen is an etiological factor in scoliosis through the deregulation of POC5.
青少年特发性脊柱侧凸（AIS）是一种复杂的三维脊柱畸形。女性 AIS 的发病率是男性的 8.4 倍。已经提出了几种关于雌激素在 AIS 进展中作用的假说。最近，中心粒蛋白基因 POC5()被确定为 AIS 的致病基因。POC5 是一种中心粒蛋白，对细胞周期进程和中心粒伸长很重要。然而，POC5 的激素调节仍有待确定。在这里，我们确定了作为雌激素受体 ERα 在正常成骨细胞（NOBs）和其他 ERα阳性细胞中调节的雌激素反应基因。通过启动子活性、基因和蛋白表达测定，我们发现 E2 通过直接基因组信号上调成骨细胞中基因的表达。我们观察到 E2 在 NOBs 和突变 AIS 成骨细胞中的不同作用。通过启动子测定，我们在近端启动子中鉴定出一个雌激素反应元件（ERE），通过 ERα 赋予雌激素反应性。雌激素还增强了 ERα 到 PO5 启动子 ERE 的募集。总之，这些发现表明雌激素通过 POC5 的失调成为脊柱侧凸的病因。
