Azeddine Bouziane, Letellier Kareen, Wang Da Shen, Moldovan Florina, Moreau Alain
Research Centre, Sainte-Justine University Hospital, Montreal, Canada.
Clin Orthop Relat Res. 2007 Sep;462:45-52. doi: 10.1097/BLO.0b013e31811f39fa.
Presently, the genetic cause of adolescent idiopathic scoliosis (AIS), the most common form of scoliosis, remains unclear. Among many hypotheses, the neuroendocrine hypothesis involving a melatonin deficiency as the source for AIS generated the greatest interest and controversy since no decrease in circulating melatonin level has been observed in a majority of studies. Previously, we have reconciled the role of melatonin in AIS by demonstrating a melatonin signaling dysfunction occurring in osteoblasts derived from AIS patients, which contrasted with similar cells isolated from healthy subjects. We found that this difference is caused in AIS cells by increased phosphorylation of serine residues affecting the activity of G inhibitory proteins normally associated with melatonin cell surface receptors. Here we propose a preliminary molecular classification of patients with AIS based on the cellular response to the melatonin (cAMP) and distinct protein-protein interactions. These interactions include those between protein kinase C delta (PKCdelta) and MT2 melatonin receptors or PKCdelta and the receptor for activated protein C kinase 1. This finding could help in future molecular classification of patients with AIS.
目前，青少年特发性脊柱侧凸（AIS）是脊柱侧凸最常见的形式，其遗传原因仍不清楚。在众多假说中，涉及褪黑素缺乏是AIS病因的神经内分泌假说引起了极大的关注和争议，因为在大多数研究中并未观察到循环褪黑素水平降低。此前，我们通过证明AIS患者来源的成骨细胞中发生褪黑素信号功能障碍，调和了褪黑素在AIS中的作用，这与从健康受试者分离的类似细胞形成对比。我们发现，AIS细胞中的这种差异是由丝氨酸残基磷酸化增加所致，这影响了通常与褪黑素细胞表面受体相关的G抑制蛋白的活性。在此，我们基于细胞对褪黑素（cAMP）的反应以及独特的蛋白质-蛋白质相互作用，提出了AIS患者的初步分子分类。这些相互作用包括蛋白激酶Cδ（PKCδ）与MT2褪黑素受体之间的相互作用，或PKCδ与活化蛋白C激酶1受体之间的相互作用。这一发现可能有助于未来对AIS患者进行分子分类。
