title: LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression.
abstract: 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-α 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-α mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF-α 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-κB inhibition.
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58, Zhongshan 2nd Road, 510080, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Hehai
authors.initials: H
authors.lastname: Pan
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Jianru
authors.initials: J
authors.lastname: Wang
authors.forename: Kuibo
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ding
authors.forename: Bingxue
authors.initials: B
authors.lastname: Li
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000517:prevention & control*; D060588:LIM Domain Proteins / Q000502:physiology*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D006025:Glycosaminoglycans; D060588:LIM Domain Proteins; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; C484380:PDLIM7 protein, human; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3
keywords: LIM Mineralization Protein-1; NF-κB; extracellular matrix; intervertebral disc degeneration; matrix metalloproteinase