Matrix metalloproteinase 12 is an indicator of intervertebral disc degeneration co-expressed with fibrotic markers

Lv, Fengxiang; Peng, Yan; Lim, Foon-Lian; Sun, Yi; Lv, Minmin; Zhou, Li; Wang, H.; Zheng, Zhaomin; Cheung, Kenneth M.C.; Leung, Victor

doi:10.1016/j.joca.2016.05.012

Cited by 45 publications

(50 citation statements)

References 38 publications

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“…6 D ). For 29 of the genes, other groups have reported that mice lacking the gene were protected against fibrosis in mouse models, including lung ( Moore et al, 2006 ; Flechsig et al, 2010 ; Riteau et al, 2010 ; Aschner et al, 2014 ; Shibata et al, 2014 ; Tan et al, 2014 ; Vuga et al, 2014 ; Agassandian et al, 2015 ; Brodeur et al, 2015 ; Wang et al, 2015 ; Lv et al, 2016 ), heart ( Li et al, 2009 ; Fan et al, 2014 ; Nishikido et al, 2016 ; Toba et al, 2016 ), liver ( Seki et al, 2009 ; Kim et al, 2010 ; Madala et al, 2010 ; Fiorotto et al, 2016 ; Marí et al, 2016 ), kidney ( Grgic et al, 2009 ; Lai et al, 2014 ; Yan et al, 2016 ), bone ( Ishizuka et al, 2011 ), eye ( Chan et al, 2013 ), muscle ( Sinadinos et al, 2015 ), and skin ( Wang et al, 2015 ). Genes exclusively expressed in TR-AMs included those involved in lipid metabolic processes and blood microparticle formation ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

Misharin

Morales‐Nebreda

Reyfman

et al. 2017

Journal of Experimental Medicine

823

917

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Section: Resultsmentioning

confidence: 99%

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

Misharin

Morales‐Nebreda

Reyfman

et al. 2017

Journal of Experimental Medicine

823

917

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“…Burke et al removed normal and degenerative nucleus pulposus for culture and found that normal and degenerative nucleus pulposus cells could spontaneously produce MCP-1 and could recruit macrophages [ 25 ]. MCP-1 has been verified to be positively correlated with the degree of lumbar intervertebral disc herniation and the degree of pain [ 26 ]. The occurrence of MCP-1 can recruit inflammatory factors and further stimulate MCP-1 expression [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…MCP-1 has been verified to be positively correlated with the degree of lumbar intervertebral disc herniation and the degree of pain [ 26 ]. The occurrence of MCP-1 can recruit inflammatory factors and further stimulate MCP-1 expression [ 26 ]. This cycle aggravates inflammatory cell infiltration and inflammatory response [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

Liang

Dai

et al. 2018

Disease Markers

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We first applied moderate fluid shear stress to nucleus pulposus cells. The correlation of AP-1 with type II collagen, proteoglycan, Cytokeratin 8 protein, MAP-1, MAP-2, and MAP-4 and the correlation of AP-1 with IL-1β, TNF-α, IL-6, IL-8, MIP-1, MCP-1, and NO were detected. Our results document that moderate fluid shear stress could activate the FAK-MEK5-ERK5-cFos-AP1 signaling pathway. AP1 could downregulate the construct factors of cytoskeleton such as type II collagen, proteoglycan, Cytokeratin 8 protein, MAP-1, MAP-2, and MAP-4 in nucleus pulposus cell after the fluid shear stress was loaded. AP1 could upregulate the inflammatory factors such as IL-1β, TNF-α, IL-6, IL-8, MIP-1, MCP-1, and NO in nucleus pulposus cell after the fluid shear stress was loaded. Taken together, our data suggested that moderate fluid shear stress may play an important role in the cytoskeleton of nucleus pulposus and surrounding inflammatory mediators by activating the FAK-MEK5-ERK5-cFos-AP1 signaling pathway, thereby affecting cell degeneration.

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“…Compared with other MMP members, MMP12 is by far the most efficient at cleaving within the aggrecan IGD 23 . Moreover, MMP12 is recently reported as an indicator of IDD that is co-expressed with fibrotic markers 28 . Tobacco smoking also strongly induces expression of MMP-12, macrophage elastase, in activated macrophages in lung tissues of smokers 25, 29 .…”

Section: Discussionmentioning

confidence: 99%

ADAMTS5 Deficiency Protects Mice From Chronic Tobacco Smoking-induced Intervertebral Disc Degeneration

Ngo

Pohl

Wang

et al. 2017

Spine

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Study Design ADAMTS5-deficient and WT mice were chronically exposed to tobacco smoke to investigate effects on intervertebral disc degeneration (IDD). Objective To demonstrate a role for ADAMTS5 in mediating tobacco smoking-induced IDD Summary of Background Data We previously demonstrated that chronic tobacco smoking causes IDD in mice due, in part, to proteolytic destruction of disc aggrecan. However, it was unknown which matrix proteinase(s) drive these detrimental effects. Methods Three-month old Wt (C57BL/6) and ADAMTS5-/- mice were chronically exposed to tobacco smoke (4 cigarettes/day, 5 day/week for 6 months). ADAMTS-mediated cleavage of disc aggrecan was analyzed by Western blot. Disc total glycosaminoglycan (GAG) content was assessed by dimethyl methylene blue assay and safranin O/fast green histology. Vertebral osteoporosity was measured by micro-computed tomography. Human nucleus pulposus (hNP) cell cultures were also exposed directly to tobacco smoke extract (TSE), a condensate containing the water-soluble compounds inhaled by smokers, to measure ADAMTS5 expression and ADAMTS-mediated cleavage of aggrecan. Activation of NF-κB, a family of transcription factors essential for modulating the cellular response to stress, was measured by immunofluorescence assay. Results Genetic depletion of ADAMTS5 prevented vertebral bone loss, substantially reduced loss of disc GAG content, and completely obviated ADAMTS-mediated proteolysis of disc aggrecan within its interglobular domain (IGD) in mice following exposure to tobacco smoke. hNP cell cultures exposed to TSE also resulted in upregulation of ADAMTS5 protein expression and a concomitant increase in ADAMTS-mediated cleavage within aggrecan IGD. Activation of NF-κB, known to be required for ADAMTS5 gene expression, was observed in both TSE-treated hNP cell cultures and disc tissue of tobacco smoke-exposed mice. Discussion The findings demonstrate that ADAMTS5 is the primary aggrecanase mediating smoking-induced disc aggrecanolysis and IDD. Mouse models of chronic tobacco smoking are important and useful for probing the mechanisms of disc aggrecan catabolism and IDD.

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Matrix metalloproteinase 12 is an indicator of intervertebral disc degeneration co-expressed with fibrotic markers

Cited by 45 publications

References 38 publications

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

ADAMTS5 Deficiency Protects Mice From Chronic Tobacco Smoking-induced Intervertebral Disc Degeneration

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