title: Matrix metalloproteinase (MMP)-3 gene up-regulation in a rat tail compression loading-induced disc degeneration model.
abstract: The rodent static compression loading-induced disc degeneration model still has important gaps among the radiographic, magnetic resonance imaging (MRI), and histological schemes and the acute and chronic expression of catabolic genes such as matrix metalloproteinase (MMP)-3. Our objectives were to assess the validity of a rat tail two-disc static compression model and to elucidate a representative catabolic marker, MMP-3 gene alterations, throughout the degenerative process. Static compression at 1.3 MPa for up to 56 days produced progressive disc height loss in radiographs, lower nucleus intensity on T2-weighted MRIs, and histomorphological degeneration. Real-time RT-PCR mRNA quantification showed significant MMP-3 up-regulation in nucleus pulposus cells from 7 days and a significantly progressive increase as the loading duration lengthened, with high correlations to radiological degenerative scores. Immunohistochemistry demonstrated progressively increased positive staining for MMP-3. These results validate this animal model for disc degeneration research. Progressive mRNA and protein-distributional up-regulations indicate the significant role of MMP-3 and its feasibility as a disc degenerative marker. This model should prove useful for investigating the pathomechanism and for evaluating molecular therapies for degenerative disc disease.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yurube
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Teppei
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneyama
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kakutani
authors.forename: Koichiro
authors.initials: K
authors.lastname: Maeno
authors.forename: Toru
authors.initials: T
authors.lastname: Takada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Minoru
authors.initials: M
authors.lastname: Doita
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055959:Intervertebral Disc Degeneration / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000000981:diagnostic imaging / Q000473:pathology; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3