LIM Mineralization Protein-1 Suppresses TNF-α Induced Intervertebral Disc Degeneration by Maintaining Nucleus Pulposus Extracellular Matrix Production and Inhibiting Matrix Metalloproteinases Expression
LIM Mineralization Protein-1 Suppresses TNF-α Induced Intervertebral Disc Degeneration by Maintaining Nucleus Pulposus Extracellular Matrix Production and Inhibiting Matrix Metalloproteinases Expression
复制标题
DOI：
10.1002/jor.22732
复制
发表时间：
2015-03-01
影响因子：
2.8
通讯作者：
Zheng, Zhaomin
中科院分区：
文献类型：
--
作者：
Liu, Hui;Pan, Hehai;Zheng, Zhaomin
髓核细胞外基质（ECM）代谢失衡与椎间盘退变密切相关。LIM矿化蛋白-1（LMP-1）已被证明诱导NP中硫酸化糖胺聚糖（sGAG）的产生，并在破骨细胞前体中具有抗炎作用。然而，它是否对炎症刺激下NP ECM的产生和降解有任何影响尚未研究。在本研究中，在体外建立了TNF诱导的细胞模型。构建编码LMP-1（LV-LMP-1）和短肝素LMP-1（LV-shLMP-1）的慢病毒以在NP细胞中过表达和敲低LMP-1表达。转染后LMP-1 mRNA水平呈剂量依赖性调节。LV-LMP-1增加，而LV-shLMP-1降低胶原II、聚集蛋白聚糖、多功能蛋白聚糖表达和sGAG产生。LV-LMP-1通过ERK 1/2激活消除TNF介导的上述基质基因的下调，而LV-shLMP-1通过ERK 1/2激活加重TNF介导的上述基质基因的下调。此外，LV-LMP-1通过抑制p65易位以及MMP-3和MMP-13启动子活性来消除TNF诱导的MMP-3和MMP-13表达。这些结果表明，LMP-1在炎症刺激下具有ECM产生维持作用。这种作用至少部分通过ERK 1/2激活上调基质基因表达，通过NF-B抑制下调MMPs表达。(c)2014骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 33：？？？-？？？，2015.
Imbalanced metabolism of Nucleus pulposus (NP) extracellular matrix (ECM) is closely correlated to Intervertebral Disc Degenerative Disease. LIM mineralization protein-1 (LMP-1) has been proven to induce sulfated glycosaminoglycan (sGAG) production in NP and have an anti-inflammatory effect in pre-osteoclast. However, whether it has any effect on the NP ECM production and degradation under inflammatory stimulation has not been studied. In the current study, a TNF- induced cell model was established in vitro. Lentivirus encoding LMP-1 (LV-LMP-1) and short heparin LMP-1 (LV-shLMP-1) were constructed to overexpress and knockdown LMP-1 expression in NP cells. LMP-1 mRNA level was regulated in a dose-dependent manner after transfection. LV-LMP-1 increased whereas LV-shLMP-1 decreased collagen II, aggrecan, versican expression, and sGAG production. LV-LMP-1 abolished while LV-shLMP-1 aggravated TNF- mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF- induced MMP-3 and MMP-13 expression via inhibiting p65 translocation and MMP-3 and MMP-13 promoter activity. These results indicated that LMP-1 had an ECM production maintenance effect under inflammatory stimulation. This effect was via up-regulation of matrix genes expression at least partially through ERK1/2 activation, and down-regulation of MMPs expression through NF-B inhibition. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???-???, 2015.