| RRC ID |
43005
|
| 著者 |
Wako M, Haro H, Ando T, Hatsushika K, Ohba T, Iwabuchi S, Nakao A, Hamada Y.
|
| タイトル |
Novel function of TWEAK in inducing intervertebral disc degeneration.
|
| ジャーナル |
J Orthop Res
|
| Abstract |
The goal of this research was to examine the role of TWEAK in normal disc cells and to investigate its potential role in disc degeneration. We performed histological examinations of disc tissues and assessed the role of the novel cytokine TWEAK using murine organ disc culture. The expression of both TWEAK and its receptor, Fn14, in discs was confirmed by immunohistochemistry and quantitative real-time PCR. TWEAK induced disc cells to generate MMP-3 in a dose- and time-dependent manner. This induction was strongly inhibited in the presence of a neutralizing antibody to TWEAK or a chimeric Fn14/Fc fusion protein. In disc tissues derived from TNF-alpha receptor 1- or TNF-alpha receptor 2-deficient mice, recombinant TWEAK modestly induced MMP-3. In contrast, in disc cultures lacking TWEAK, tissues from wild-type mice or receptor-deficient mice failed to express MMP-3. Furthermore, aggrecan expression was potently abrogated in a time-dependent manner in the presence of recombinant TWEAK. This is the first report to confirm expression of TWEAK and its receptor Fn14 in murine intervertebral disc tissues. The data suggest that TWEAK plays a role in MMP-3 up-regulation and aggrecan down-regulation in disc tissues, resulting in proteoglycan degradation and promotion of disc degeneration.
|
| 巻・号 |
25(11)
|
| ページ |
1438-46
|
| 公開日 |
2007-11-1
|
| DOI |
10.1002/jor.20445
|
| PMID |
17568422
|
| MeSH |
Aggrecans / metabolism
Animals
Antibodies, Blocking / pharmacology
Cytokine TWEAK
Enzyme Induction / drug effects
Gene Expression Regulation / drug effects
Gene Silencing
Immunoenzyme Techniques
Intervertebral Disc / drug effects
Intervertebral Disc / metabolism*
Intervertebral Disc / pathology
Intervertebral Disc Displacement*
Matrix Metalloproteinase 3 / biosynthesis
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Tumor Necrosis Factor / deficiency
Receptors, Tumor Necrosis Factor / genetics
Receptors, Tumor Necrosis Factor / metabolism
Receptors, Tumor Necrosis Factor, Type I / deficiency
Receptors, Tumor Necrosis Factor, Type I / genetics
Recombinant Proteins / pharmacology
TWEAK Receptor
Tumor Necrosis Factors / genetics
Tumor Necrosis Factors / immunology
Tumor Necrosis Factors / metabolism*
Tumor Necrosis Factors / pharmacology
|
| IF |
2.728
|
| 引用数 |
9
|
|
WOS 分野
|
ORTHOPEDICS
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126)
ATDC5(RCB0565) |
