Hepatocyte growth factor/c-met promotes proliferation, suppresses apoptosis, and improves matrix metabolism in rabbit nucleus pulposus cells in vitro
Hepatocyte growth factor/c-met promotes proliferation, suppresses apoptosis, and improves matrix metabolism in rabbit nucleus pulposus cells in vitro
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DOI：
10.1002/jor.23063
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发表时间：
2016-04-01
影响因子：
2.8
通讯作者：
Kubo, Toshikazu
中科院分区：
文献类型：
--
作者：
Ishibashi, Hidenobu;Tonomura, Hitoshi;Kubo, Toshikazu
椎间盘退变的病因与髓核细胞凋亡和细胞外基质降解密切相关。NP细胞中的这些缺陷由过度的外部应激源如活性氧（ROS）和炎性细胞因子诱导。最近，肝细胞生长因子（HGF）已被证明可以通过抗凋亡和抗炎活性来修复各种疾病中的损伤。本研究利用兔IVD原代培养的NP细胞，观察HGF对ROS和炎性细胞因子引起的NP细胞异常的影响。HGF可明显促进NP细胞的增殖。HGF可明显抑制H_2O_2或TNF-α诱导的NP细胞凋亡。TNF-α诱导的炎症介质环氧合酶-2和基质金属蛋白酶-3和-9的mRNA表达被HGF治疗显著抑制。在NP细胞中证实了HGF的特异性受体c-Met的表达，并且通过TNF-α增加，表明炎性细胞因子增加对HGF的敏感性。这些发现表明HGF/c-Met信号传导的激活通过多种途径抑制了NP细胞中由ROS和炎症引起的损伤。我们进一步表明HGF对抗NP细胞异常所涉及的IVD降解的临床潜力。(c)2015骨科研究学会。由威利期刊公司出版J Orthop Res 34：709-716，2016.
The etiology of intervertebral disc (IVD) degeneration is closely related to apoptosis and extracellular matrix degradation in nucleus pulposus (NP) cells. These defects in NP cells are induced by excessive external stressors such as reactive oxygen species (ROS) and inflammatory cytokines. Recently, hepatocyte growth factor (HGF) has been shown to repair damage in various diseases through anti-apoptotic and anti-inflammatory activity. In this study, we investigated the effects of HGF on NP cell abnormality caused by ROS and inflammatory cytokines by using primary NP cells isolated from rabbit IVD. HGF significantly enhanced the proliferation of NP cells. Apoptosis of NP cells induced by H2O2 or TNF- was significantly inhibited by HGF. Induction of mRNA expression of the inflammation mediators cyclooxygenase-2 and matrix metalloproteinase-3 and -9 by TNF- was significantly suppressed by HGF treatment. Expression of c-Met, a specific receptor for HGF, was confirmed in NP cells and was increased by TNF-, suggesting that inflammatory cytokines increase sensitivity to HGF. These findings demonstrate that activation of HGF/c-Met signaling suppresses damage caused by ROS and inflammation in NP cells through multiple pathways. We further suggest the clinical potential of HGF for counteracting IVD degradation involved in NP cell abnormalities. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:709-716, 2016.