| RRC ID |
57841
|
| 著者 |
Duan L, Duan D, Wei W, Sun Z, Xu H, Guo L, Wu X.
|
| タイトル |
MiR-19b-3p attenuates IL-1β induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6.
|
| ジャーナル |
Mol Cell Biochem
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| Abstract |
Osteoarthritis (OA) is characterized by degradation of articular cartilage. MiRNAs are involved in the regulation of chondrogenesis and OA. We aimed to investigate effects and mechanisms of miR-19b-3p in regulating chondrocytes viability, cartilage degradation and inflammatory response. Primary chondrocytes were isolated from cartilages in control subjects and patients with OA. Murine ATDC5 cells were pre-conditioned with IL-1β in vitro. Expressions and interaction of miR-19b-3p with G protein-coupled receptor kinase 6 (GRK6), and their effects on inflammation, chondrocytes viability and cartilage degradation were determined after miR-19b-3p mimic or GRK6 siRNA transfection. MiR-19b-3p was significantly decreased in OA chondrocytes and IL-1β-stimulated ATDC5 cells, in paralleled with the elevated type-II-collagen, aggrecan, MMP13 and GRK6 expression. MiR-19b-3p mimic dramatically increased the viability of chondrocytes and suppressed cell apoptosis. It also increased type-II-collagen, aggrecan expression and glycosaminoglycan (sGAG) content, and decreased the expression of MMP-1 and MMP-13 that controlled by IL-1β. Overexpression of miR-19b-3p inhibited the production of IL-6 and IL-8 in ATDC5 cells. However, the protective effects of miR-19b-3p mimic on IL-1β induced cell death; IL-8 production and sGAG decrease were greatly discounted by GRK6 lentiviral vectors. Luciferase reporter assay confirmed that GRK6 gene was a direct target ofmiR-19b-3p. GRK6 siRNA transfection antagonized the IL-1β-induced chondrocytes injury, extracellular matrix degradation and inflammatory response. MiR-19b-3p mimic and GRK6 siRNA showed comparable inhibitory effect on IL-1β-provoked NF-κB as reflected by the expression of p-p65. NF-κB translocation inhibition with PS1154 reversed the effects of IL-1β on IL-8 and sGAG. Collectively, miR-19b-3p attenuated OA by targeting GRK6-NF-κB pathway.
|
| 巻・号 |
459(1-2)
|
| ページ |
205-214
|
| 公開日 |
2019-9-1
|
| DOI |
10.1007/s11010-019-03563-2
|
| PII |
10.1007/s11010-019-03563-2
|
| PMID |
31227976
|
| MeSH |
Aged
Cell Line
Chondrocytes / metabolism*
Chondrocytes / pathology
Extracellular Matrix / metabolism*
Extracellular Matrix / pathology
Female
G-Protein-Coupled Receptor Kinases / metabolism*
Humans
Inflammation / metabolism
Inflammation / pathology
Interleukin-1beta / metabolism*
Male
MicroRNAs / metabolism*
Middle Aged
Osteoarthritis, Knee / metabolism*
Osteoarthritis, Knee / pathology
Signal Transduction
|
| IF |
2.795
|
| 引用数 |
2
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
