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LIM mineralization protein‐1 suppresses TNF‐α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression
Author(s) -
Liu Hui,
Pan Hehai,
Yang Hao,
Wang Jianru,
Zhang Kuibo,
Li Xiang,
Wang Hua,
Ding Wenbin,
Li Bingxue,
Zheng Zhaomin
Publication year - 2015
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22732
Subject(s) - matrix metalloproteinase , extracellular matrix , gene knockdown , aggrecan , microbiology and biotechnology , chemistry , versican , mmp9 , intervertebral disc , proteoglycan , stimulation , transfection , downregulation and upregulation , biology , endocrinology , gene , medicine , biochemistry , anatomy , pathology , osteoarthritis , articular cartilage , alternative medicine
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. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???–???, 2015.