論文 - 詳細
| RRC ID | 44604 |
|---|---|
| 著者 | Kobayashi H, Hirata M, Saito T, Itoh S, Chung UI, Kawaguchi H. |
| タイトル | Transcriptional induction of ADAMTS5 protein by nuclear factor-κB (NF-κB) family member RelA/p65 in chondrocytes during osteoarthritis development. |
| ジャーナル | J Biol Chem |
| Abstract |
Here we sought to identify transcription factors that induce ADAMTS5, a crucial proteinase for osteoarthritis development. Exhaustive comparison of the genomic sequences of human, macaque, and mouse ADAMTS5 genes revealed that the proximal 1.4 kb of the 5'-end-flanking regions containing several consensus motifs was highly conserved. Among putative transcription factors for these motifs, NF-κB family member RelA/p65 most strongly stimulated the promoter activity. In the ADAMTS5 gene, there were three NF-κB binding motifs, in which deletion, mutagenesis, and tandem repeat analyses of the luciferase assay identified the core responsive elements of RelA/p65 to be -896/-887 and -424/-415 bp with specific bindings. The endogenous Adamts5 expression in ATDC5 cells was increased by RelA/p65 overexpression and decreased by knockdown through its siRNA. The expression was also inhibited by the Rela deletion through Cre transfection in primary articular chondrocytes from Rela(fl/fl) mice. In the ex vivo culture of femoral head cartilage from mesenchymal cell-specific Rela knock-out (Prx1-Cre;Rela(fl/fl)) mice, aggrecanolysis was significantly lower than that in the Rela(fl/fl) cartilage. Finally, in the experimental mouse osteoarthritis model, ADAMTS5 and RelA were co-localized in chondrocytes of degraded articular cartilage. We conclude that RelA/p65 is a potent transcriptional activator of ADAMTS5 in chondrocytes during osteoarthritis development. |
| 巻・号 | 288(40) |
| ページ | 28620-9 |
| 公開日 | 2013-10-4 |
| DOI | 10.1074/jbc.M113.452169 |
| PII | S0021-9258(20)48837-4 |
| PMID | 23963448 |
| PMC | PMC3789961 |
| MeSH | ADAM Proteins / genetics* ADAM Proteins / metabolism ADAMTS5 Protein Aggrecans / metabolism Animals Base Sequence Cartilage, Articular / metabolism Cartilage, Articular / pathology Cell Line Chondrocytes / enzymology* Chondrocytes / pathology Humans Immunohistochemistry Macaca Mice Molecular Sequence Data Osteoarthritis / enzymology* Osteoarthritis / genetics* Osteoarthritis / pathology Promoter Regions, Genetic / genetics Protein Transport Sequence Homology, Nucleic Acid Trans-Activators / metabolism Transcription Factor RelA / metabolism* Transcription, Genetic* |
| IF | 4.238 |
| 引用数 | 33 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |