| 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
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
