論文 - 詳細
| RRC ID | 62043 |
|---|---|
| 著者 | Otsuki S, Murakami T, Okamoto Y, Hoshiyama Y, Oda S, Neo M. |
| タイトル | Suppression of cartilage degeneration by intra-articular injection of heparan sulfate 6-O endosulfatase in a mouse osteoarthritis model. |
| ジャーナル | Histol Histopathol |
| Abstract |
We previously reported that heparan sulfate 6-O endosulfatases (Sulfs) were expressed in articular cartilage, and that the Sulf-1 knockout mouse developed severe knee osteoarthritis. In this study, we hypothesised that intra-articular injection of Sulf-1 would prevent cartilage degeneration. After confirming that 1 mg/ml Sulf-1 did not induce ATDC5 cell death in vitro, gene expression of type II collagen and matrix metalloproteinase (MMP)-13 in the presence of Sulf-1 (1 100 ng/ml) were determined by quantitative real-time polymerase chain reaction. Sulf-1 was also injected intra-articularly into mice following surgical destabilisation of the medial meniscus to produce a model of osteoarthritis, and cartilage degeneration was evaluated by safranin O and MMP-13 staining. We also investigated fibroblast growth factor 2 (FGF2)/extracellular signal-regulated kinase (Erk) cell signalling by western blotting. Exposure to Sulf-1 in vitro increased type II collagen expression and decreased MMP-13 expression in a concentration-dependent manner. Sulf-1 injection into the mouse osteoarthritic knee significantly suppressed glycosaminoglycan loss and MMP-13 expression. Erk1/2 signalling pathway activation was significantly reduced by Sulf-1 and FGF2. These findings indicate that Sulf-1 prevents cartilage degeneration by suppressing MMP-13 via an effect on FGF2/Erk1/2 signalling. |
| 巻・号 | 32(7) |
| ページ | 725-733 |
| 公開日 | 2017-7-1 |
| DOI | 10.14670/HH-11-838 |
| PII | HH-11-838 |
| PMID | 27808352 |
| MeSH | Animals Cartilage, Articular / cytology Cartilage, Articular / pathology* Cell Line Cell Survival Collagen Type II / biosynthesis Collagen Type II / genetics Fibroblast Growth Factor 2 / biosynthesis Gene Expression Regulation / drug effects Gene Expression Regulation / genetics Immunohistochemistry Injections, Intra-Articular MAP Kinase Signaling System / drug effects Male Matrix Metalloproteinase 13 / biosynthesis Matrix Metalloproteinase 13 / genetics Mice Mice, Inbred C57BL Mice, Knockout Osteoarthritis / drug therapy* Osteoarthritis / pathology* Sulfotransferases / administration & dosage Sulfotransferases / genetics Sulfotransferases / therapeutic use* |
| IF | 2.021 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |