title: Matrix metalloproteinase-26, a novel MMP, is constitutively expressed in the human intervertebral disc in vivo and in vitro.
abstract: Matrix metalloproteinase (MMP) regulation and expression is important in the aging/degenerating human intervertebral disc. MMP-26 (also known as matrilysin-2 or endometase) is a newly discovered MMP which degrades type IV collagen, fibronectin, fibrinogen, vitronectin, denatured collagen types I-IV, insulin-like growth factor binding protein 1, and activated pro-MMP-9. Our objective here was to determine if it is present in human disc tissue and cultured disc cells. Immunohistochemistry and microarray gene expression analyses were used to evaluate the presence of MMP-26 in human disc tissue from healthy and degenerated discs. Immunohistochemistry was also applied to human annulus cells cultured in a collagen sponge. Cellular and matrix localization of MMP-26 was identified in the outer and inner annulus and in the nucleus pulposus. Fewer cells showed localization in the inner vs. outer annulus, and localization was sparse in the nucleus. During in vitro culture of annulus cells, MMP-26 was also expressed. Molecular analyses showed significant downregulation of expression of MMP-26 (p=0.03), and significant 9.8-fold upregulation of TGF-beta (p=0.01) in more degenerated discs vs. healthier discs. Findings document the first identification of MMP-26 in the disc at the molecular and protein levels. Results point to the potentially important role of MMP-26 in matrix modulation during disc health and degeneration.
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232, USA. helen.gruber@carolinashealthcare.org
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Hoelscher
authors.forename: Jane A
authors.initials: JA
authors.lastname: Ingram
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007403:Intervertebral Disc / Q000166:cytology / Q000201:enzymology*; D055959:Intervertebral Disc Degeneration / Q000201:enzymology* / Q000473:pathology; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D016212:Transforming Growth Factor beta; C410599:MMP26 protein, human; D053505:Matrix Metalloproteinases, Secreted