Matrix metalloproteinase (MMP)-3 gene up-regulation in a rat tail compression loading-induced disc degeneration model.
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.
Yurube
Takashi
T
Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Nishida
Kotaro
K
Suzuki
Teppei
T
Kaneyama
Shuichi
S
Zhang
Zhongying
Z
Kakutani
Kenichiro
K
Maeno
Koichiro
K
Takada
Toru
T
Fujii
Masahiko
M
Kurosaka
Masahiro
M
Doita
Minoru
M
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
D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3