Department of Orthopedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
J Pineal Res. 2011 May;50(4):395-402. doi: 10.1111/j.1600-079X.2011.00857.x. Epub 2011 Feb 24.
Melatonin signaling dysfunction has been associated with the etiology of adolescent idiopathic scoliosis (AIS). Genetic analysis has also associated the occurrence of AIS with the MT2 gene. Thus, we determined whether there is abnormality in the protein expression of melatonin receptors (MT) in AIS osteoblasts. In this study, we recruited 11 girls with severe AIS and eight normal subjects for intraoperative bone biopsies. MT1 and MT2 receptor protein expressions in the isolated osteoblasts were detected. Also, cell proliferation assay using different melatonin concentrations (0, 10(-9), 10(-5), 10(-4) m) was carried out. The results showed that both MT1 and MT2 receptors are expressed in osteoblasts of the controls. While MT1 receptors were expressed in osteoblasts of all AIS subjects, osteoblasts of only 7 of 11 AIS showed expression of MT2 receptors. Melatonin stimulated control osteoblasts to proliferate. However, proliferation of AIS osteoblasts without expression of MT2 receptor, after treatment with melatonin, was minimal when compared with control and AIS osteoblasts with MT2 receptor expression. The proliferation of AIS osteoblasts with MT2 receptor was greater than those without. This is the first report demonstrating a difference between AIS and normal osteoblasts in the protein expression of MT2 receptor. The results suggest that there is a possible functional effect of MT2 receptor on osteoblast proliferation. AIS osteoblasts without expression of MT2 receptor showed the lowest percentage of viable cells after melatonin treatment. This possibly indicates the modulating role of melatonin through MT2 receptor on the proliferation of osteoblasts.
褪黑素信号功能障碍与青少年特发性脊柱侧凸（AIS）的病因有关。遗传分析也将 AIS 的发生与 MT2 基因联系起来。因此，我们确定 AIS 成骨细胞中褪黑素受体（MT）的蛋白表达是否存在异常。在这项研究中，我们招募了 11 名患有严重 AIS 的女孩和 8 名正常受试者进行术中骨活检。检测了分离的成骨细胞中 MT1 和 MT2 受体蛋白的表达。还进行了使用不同褪黑素浓度（0、10（-9）、10（-5）、10（-4）m）的细胞增殖测定。结果表明，MT1 和 MT2 受体均在对照组的成骨细胞中表达。虽然 MT1 受体在所有 AIS 患者的成骨细胞中均有表达，但只有 11 名 AIS 患者中的 7 名成骨细胞表达 MT2 受体。褪黑素刺激对照组成骨细胞增殖。然而，与对照组和表达 MT2 受体的 AIS 成骨细胞相比，无 MT2 受体表达的 AIS 成骨细胞在褪黑素处理后增殖最小。表达 MT2 受体的 AIS 成骨细胞的增殖大于无表达 MT2 受体的成骨细胞。这是第一项表明 MT2 受体蛋白表达在 AIS 和正常成骨细胞之间存在差异的报告。结果表明，MT2 受体对成骨细胞增殖可能存在功能影响。无 MT2 受体表达的 AIS 成骨细胞在用褪黑素处理后显示出最低的活细胞百分比。这可能表明褪黑素通过 MT2 受体对成骨细胞增殖的调节作用。
