Wang Yun-Jia, Yu Hong-Gui, Zhou Zhen-Hai, Guo Qiang, Wang Long-Jie, Zhang Hong-Qi
Department of Spine Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, China.
Int J Mol Sci. 2016 Jul 20;17(7):1160. doi: 10.3390/ijms17071160.
To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.
为了探究青少年特发性脊柱侧凸（AIS）女孩来源的原代软骨细胞代谢活性低的潜在机制；AIS是一种常发生于女孩的脊柱畸形疾病。AIS与比健康个体更低的骨量以及骨质减少有关。瘦素已被证明在骨骼生长中起重要作用。它还可以调节软骨细胞的功能。多项研究报道了AIS患者中瘦素和Ob-R水平的变化。外周瘦素信号功能障碍与软骨细胞异常之间的潜在机制仍不清楚；在AIS患者和对照组中评估了以下参数：血清总瘦素水平；原代软骨细胞质膜上的Ob-R表达；JAK2和STAT3的磷酸化状态。然后，我们抑制了溶酶体和蛋白酶体，并敲低了从AIS女孩分离的原代软骨细胞中网格蛋白重链（CHC）的表达，并评估Ob-R表达。我们研究了瘦素与溶酶体抑制剂联合或CHC敲低对从AIS患者获得的原代软骨细胞的影响；与对照组相比，AIS患者的血清总瘦素水平相似，JAK2和STAT3磷酸化降低，小关节软骨基质合成减少。在AIS组的原代软骨细胞中观察到比对照组更低的代谢活性和更低的Ob-R膜表达。溶酶体抑制增加了总Ob-R含量，但对Ob-R的膜表达或瘦素对AIS原代软骨细胞的作用没有影响。CHC敲低上调了膜Ob-R水平并增强了瘦素对AIS原代软骨细胞的作用；在一些AIS女孩中，软骨细胞对瘦素低敏的潜在机制是质膜Ob-R表达低，这是由于受体内吞速率与新合成受体插入膜的速率之间的不平衡所致。
