論文 - 詳細
| RRC ID | 43993 |
|---|---|
| 著者 | Andrés-Bergós J, Tardio L, Larranaga-Vera A, Gómez R, Herrero-Beaumont G, Largo R. |
| タイトル | The increase in O-linked N-acetylglucosamine protein modification stimulates chondrogenic differentiation both in vitro and in vivo. |
| ジャーナル | J Biol Chem |
| Abstract |
Insulin is an inducer of chondrocyte hypertrophy and growth plate chondrogenesis, although the specific molecular mechanisms behind these effects are mostly unknown. Our aim was to investigate whether insulin-induced chondrocyte hypertrophy occurs through a modification in the amount of O-linked N-acetylglucosamine (O-GlcNAc)-modified proteins and in the expression of the key enzymes of this pathway, O-GlcNAc transferase and O-GlcNAcase (OGA). We also studied if O-GlcNAc accumulation per se, induced by an OGA inhibitor, was able to induce pre-hypertrophic chondrocyte differentiation both in vitro and in vivo. Insulin-induced differentiation of ATDC5 pre-chondrocytes occurred alongside a gradual increase in the accumulation of O-GlcNac-modified proteins (O-GlcNAcylated proteins), as well as an increase in the expression of O-GlcNAc transferase and OGA. In the absence of insulin, O-GlcNAc accumulation induced by thiamet-G, a specific OGA inhibitor, was able to increase the gene expression of differentiation markers, as well as the activity of MMP-2 and -9. Thiamet-G also activated pERK, p-JNK, and p-p38 and the O-GlcNAcylation of Akt. Thiamet-G administration to C57/bl mice induced a significant expansion in the growth plate height and in the hypertrophic zone height. Therefore, our results show that O-GlcNAc glycosylation has chondromodulating activity. |
| 巻・号 | 287(40) |
| ページ | 33615-28 |
| 公開日 | 2012-9-28 |
| DOI | 10.1074/jbc.M112.354241 |
| PII | S0021-9258(20)62863-0 |
| PMID | 22859309 |
| PMC | PMC3460460 |
| MeSH | Acetylglucosamine / chemistry* Animals Cell Differentiation Cell Line Chondrocytes / cytology* Chondrocytes / metabolism Gene Expression Regulation, Enzymologic Hypertrophy In Vitro Techniques Insulin / metabolism Male Matrix Metalloproteinases / metabolism Mice Mice, Inbred C57BL N-Acetylglucosaminyltransferases / metabolism* Signal Transduction Tissue Distribution |
| IF | 4.238 |
| 引用数 | 47 |
| 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 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 6.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |