Ghrelin up-regulates cartilage-specific genes via the ERK/STAT3 pathway in chondrocytes of patients with adolescent idiopathic scoliosis
Ghrelin up-regulates cartilage-specific genes via the ERK/STAT3 pathway in chondrocytes of patients with adolescent idiopathic scoliosis
复制标题
Ghrelin 通过 ERK/STAT3 通路上调青少年特发性脊柱侧凸患者软骨细胞中的软骨特异性基因。
DOI：
10.1016/j.bbrc.2019.08.044
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发表时间：
2019-10-15
影响因子：
3.1
通讯作者：
Zhang, Hong-Qi
中科院分区：
文献类型：
--
作者：
Liang, Zhuo-Tao;Li, Jiong;Zhang, Hong-Qi
青少年特发性脊柱侧凸(AIS)是一种严重的脊柱畸形，常发生在青春期。AIS的发生可能与软骨发育异常有关。我们先前的研究发现，AIS患者血清Ghrelin水平升高可能与AIS的发生有关。然而，Ghrelin是否影响AIS患者的软骨尚不清楚。采用实时定量聚合酶链式反应(qRT-PCR)和免疫组织化学方法检测软骨特异性基因和生长激素促分泌素受体(GHSR)的表达。AIS组II型胶原(COLII)、SOX9、AGGRECAN(Acan)和GHSR的mRNA和蛋白水平均高于对照组。此外，GHSR下游信号通路成员p-STAT3(Ser727)和p-ERK1/2的蛋白水平增加。此外，我们用100 nM的Ghrelin处理AIS患者的软骨细胞，细胞增殖实验和Western blotting显示Ghrelin促进软骨细胞的增殖，并分别促进COLII、SOX9、ACAN、p-ERK1/2和p-STAT3的表达。有趣的是，所有这些观察到的改变都被Ghrelin+[D-Lys3]-GHRP-6(一种Ghrelin受体抑制剂)处理所消除。经ERK1/2磷酸化抑制剂U0126处理后，ERK1/2和STAT3(Ser727)的磷酸化同时被抑制，表明ERK1/2是STAT3(Ser727)的上游途径蛋白。总之，Ghrelin通过激活ERK/STAT3信号通路，在上调AIS原代软骨细胞软骨特异性基因表达中发挥重要作用。(C)2019 Elsevier Inc.保留所有权利。
Adolescent idiopathic scoliosis (AIS) is a severe spinal deformity that often occurs during puberty. The occurrence of AIS is suggested to be related to abnormal development of cartilage. Our previous study found increased serum ghrelin levels in AIS patients that may linked to the development of AIS. However, whether ghrelin affects cartilage in AIS patients is unclear. We used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to detect the expression of cartilage-specific genes and the ghrelin receptor, growth hormone secretagogue receptor (GHSR). The mRNA and protein levels of collagen II (COLII), SOX9, AGGRECAN (ACAN) and GHSR were higher in AIS patients than in controls. In addition, the protein levels of GHSR downstream signaling pathway members p-STAT3 (Ser727), and p-ERK1/2 were increased. Furthermore, we treated chondrocytes from AIS patients with 100 nM ghrelin, the cell proliferation assay and Western blotting showed that ghrelin promotes chondrocyte proliferation and enhances COLII, SOX9, ACAN, p-ERK1/2 and p-STAT3 expression, respectively. Interestingly, all these observed alterations were abolished by ghrelin + [D-Lys3]-GHRP-6 (a ghrelin receptor inhibitor) treatment. And after U0126 (an inhibitor of ERK1/2 phosphorylation) treatment, ERK1/2 and STAT3 (Ser727) phosphorylation was simultaneously suppressed indicating that ERK1/2 is an upstream pathway protein of STAT3 (Ser727). In conclusion, ghrelin plays an important role in upregulating cartilage-specific genes on AIS primary chondrocytes by activating ERK/STAT3 signaling pathway. (C) 2019 Elsevier Inc. All rights reserved.