Icariin possesses chondroprotective efficacy in a rat model of dexamethasone-induced cartilage injury through the activation of miR-206 targeting of cathepsin K.
Int J Mol Med
; 41(2): 1039-1047, 2018 Feb.
Article
em En
| MEDLINE
| ID: mdl-29207029
ABSTRACT
The present study aimed to investigate the articular cartilage and chondrocytes of dexamethasone (DXM)-induced cartilage injuries in rats in response to treatment with icariin, as well as the implicated molecular mechanism. Effects of icariin on bone metabolism and articular cartilage in experimental rats were investigated. Subsequently, the present study assessed dysregulated microRNA (miRNA) in the articular cartilage of experimental rats, and validated the significant miRNA and their targets. Finally, the effects of icariin on chondrocytes in experimental rats and the implicated molecular mechanism were explored. Quantitative polymerase chain reaction demonstrated that icariin significantly reversed DXM-induced bone degradation and stimulated bone regeneration. In addition, some notable changes in articular cartilage were also observed following continuous administration of icariin to DXM-treated rats, including enhanced cartilage area (revealed by safranin-O staining), substantial decrements in serum concentrations of deoxypyridinoline and C-terminal telopeptide of type II collagen, reduced expression of collagen type I and matrix metalloproteinase-13, as well as elevated expression of transforming growth factor-ß. Furthermore, miR-206 was determined to be significantly upregulated in the icariin group compared with the DXM-treated group. A luciferase assay further validated cathepsin K as the target RNA of miR-206. Additionally, icariin (100 µM) facilitated the viability of chondrocytes and reduced apoptotic chondrocytes. More importantly, icariin (100 µM) not only abolished the inhibition effect of DXM on miR-206 expression in chondrocytes, but also eliminated the enhancing effect of DXM on cathepsin K expression. Overall, the present study identified icariin as a novel therapeutic agent in DXM-induced cartilage injury in rats, and revealed that the activation of miR-206 targeting of cathepsin K may be responsible for the chondroprotective efficacy of icariin.
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Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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Cartilagem Articular
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Condrócitos
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MicroRNAs
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Catepsina K
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article