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

TitleMatrix metalloproteinase 12 is an indicator of intervertebral disc degeneration co-expressed with fibrotic markers
Authors
KeywordsIntervertebral disc
Degeneration
Nucleus pulposus
Matrix metalloproteinase
MMP12
Issue Date2016
PublisherWB Saunders Co Ltd. The Journal's web site is located at http://www.elsevier.com/locate/joca
Citation
Osteoarthritis and Cartilage, 2016, v. 24 n. 10, p. 1826-1836 How to Cite?
AbstractObjective Recent evidence suggests a role of fibrogenesis in intervertebral disc (IVD) degeneration. We aim to explore if fibrotic genes may serve as IVD degeneration indicators, and if their expression is associated with myofibroblast activity. Design Transcriptional expression of fibrosis markers (COL1A1, COL3A1, FN1, HSP47, MMP12, RASAL1) were analyzed in degenerated (D) and non-degenerated (ND) human nucleus pulposus (NP) and annulus fibrosus (AF) cells, along with traditional (SOX9, ACAN) and newly established degeneration markers (CDH2, KRT19, KRT18, FBLN1, MGP, and COMP). Protein expression was investigated by immunohistochemistry in human IVDs, and in rodent IVDs undergoing natural ageing or puncture-induced degeneration. Co-expression with myofibroblast markers was examined by double staining on human and rat specimens. Disc degeneration severity and extent of fibrosis were determined by histological scoring and picrosirius red staining respectively. Results Human D-NP showed more intensive staining for picrosirius red than ND-NP. Among the genes examined, D-NP showed significantly higher MMP12 expression along with lower KRT19 expression. Protein expression analysis revealed increased MMP12(+) cells in human D-IVD. Histological scoring indicated mild degeneration in the punctured rat discs and discs of ageing mouse. Higher MMP12 positivity was found in peripheral NP and AF of the degenerative rat discs and in NP of the aged mice. In addition, human D-NP and D-AF showed increased α-SMA(+) cells, indicating enhanced myofibroblast activity. MMP12 was found co-expressed with α-SMA, FSP1 and FAP-α in human and rat degenerative IVDs. Conclusions Our study suggests that in addition to a reduced KRT19 expression, an increased expression of MMP12, a profibrotic mediator, is characteristic of disc degenerative changes. Co-expression study indicates an association of the increased MMP12 positivity with myofibroblast activity in degenerated IVDs. Overall, our findings implicate an impact of MMP12 in disc cell homeostasis. The precise role of MMP12 in IVD degeneration warrants further investigation.
Persistent Identifierhttp://hdl.handle.net/10722/231191
ISSN
2019 Impact Factor: 4.793
2015 SCImago Journal Rankings: 1.901
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLv, F-
dc.contributor.authorPeng, Y-
dc.contributor.authorLim, FL-
dc.contributor.authorSun, Y-
dc.contributor.authorZhou, L-
dc.contributor.authorWang, H-
dc.contributor.authorZheng, Z-
dc.contributor.authorCheung, KMC-
dc.contributor.authorLeung, VYL-
dc.date.accessioned2016-09-20T05:21:19Z-
dc.date.available2016-09-20T05:21:19Z-
dc.date.issued2016-
dc.identifier.citationOsteoarthritis and Cartilage, 2016, v. 24 n. 10, p. 1826-1836-
dc.identifier.issn1063-4584-
dc.identifier.urihttp://hdl.handle.net/10722/231191-
dc.description.abstractObjective Recent evidence suggests a role of fibrogenesis in intervertebral disc (IVD) degeneration. We aim to explore if fibrotic genes may serve as IVD degeneration indicators, and if their expression is associated with myofibroblast activity. Design Transcriptional expression of fibrosis markers (COL1A1, COL3A1, FN1, HSP47, MMP12, RASAL1) were analyzed in degenerated (D) and non-degenerated (ND) human nucleus pulposus (NP) and annulus fibrosus (AF) cells, along with traditional (SOX9, ACAN) and newly established degeneration markers (CDH2, KRT19, KRT18, FBLN1, MGP, and COMP). Protein expression was investigated by immunohistochemistry in human IVDs, and in rodent IVDs undergoing natural ageing or puncture-induced degeneration. Co-expression with myofibroblast markers was examined by double staining on human and rat specimens. Disc degeneration severity and extent of fibrosis were determined by histological scoring and picrosirius red staining respectively. Results Human D-NP showed more intensive staining for picrosirius red than ND-NP. Among the genes examined, D-NP showed significantly higher MMP12 expression along with lower KRT19 expression. Protein expression analysis revealed increased MMP12(+) cells in human D-IVD. Histological scoring indicated mild degeneration in the punctured rat discs and discs of ageing mouse. Higher MMP12 positivity was found in peripheral NP and AF of the degenerative rat discs and in NP of the aged mice. In addition, human D-NP and D-AF showed increased α-SMA(+) cells, indicating enhanced myofibroblast activity. MMP12 was found co-expressed with α-SMA, FSP1 and FAP-α in human and rat degenerative IVDs. Conclusions Our study suggests that in addition to a reduced KRT19 expression, an increased expression of MMP12, a profibrotic mediator, is characteristic of disc degenerative changes. Co-expression study indicates an association of the increased MMP12 positivity with myofibroblast activity in degenerated IVDs. Overall, our findings implicate an impact of MMP12 in disc cell homeostasis. The precise role of MMP12 in IVD degeneration warrants further investigation.-
dc.languageeng-
dc.publisherWB Saunders Co Ltd. The Journal's web site is located at http://www.elsevier.com/locate/joca-
dc.relation.ispartofOsteoarthritis and Cartilage-
dc.rightsPosting accepted manuscript (postprint): © <year>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectIntervertebral disc-
dc.subjectDegeneration-
dc.subjectNucleus pulposus-
dc.subjectMatrix metalloproteinase-
dc.subjectMMP12-
dc.titleMatrix metalloproteinase 12 is an indicator of intervertebral disc degeneration co-expressed with fibrotic markers-
dc.typeArticle-
dc.identifier.emailLv, F: fengjuan@hku.hk-
dc.identifier.emailCheung, KMC: cheungmc@hku.hk-
dc.identifier.emailLeung, VYL: vicleung@hku.hk-
dc.identifier.authorityCheung, KMC=rp00387-
dc.identifier.authorityLeung, VYL=rp01764-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.joca.2016.05.012-
dc.identifier.pmid27211863-
dc.identifier.scopuseid_2-s2.0-84990889348-
dc.identifier.hkuros263205-
dc.identifier.volume24-
dc.identifier.issue10-
dc.identifier.spage1826-
dc.identifier.epage1836-
dc.identifier.isiWOS:000384130400017-
dc.publisher.placeUnited Kingdom-

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