Identification of microRNA3633p as an essential regulator of chondrocyte apoptosis in osteoarthritis by targeting NRF1 through the p53signaling pathway.
Mol Med Rep
; 21(3): 1077-1088, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-32016449
ABSTRACT
Osteoarthritis (OA) is a degenerative joint disease that affects the physical, and mental health of middleaged and elderly people. The aims of the present study were to determine the biological function and molecular mechanisms of miR3633p in chondrocyte apoptosis. Exploration of the molecular mechanisms of OA may be helpful in the understand of the causes, and facilitating the prevention and treatment of OA. In the present study, the expression of nuclear respiratory factor1 (NRF1) was downregulated in the articular cartilage of OA rats in vivo and lipopolysaccharide (LPS)treated chondrocytes in vitro. MicroRNAs (miRNA) are regulators of gene expression in the progression of OA. TargetScan software was used to predict that NRF1 was a potential target for miRNA (miR)363, and this was confirmed in subsequent experiments. The expression of miR3633p was negatively correlated with the expression of NRF1, and its expression was significantly upregulated in OA model rats and in LPSinduced chondrocytes compared with the expression in the respective controls. In addition, the overexpression of miR3633p increased the levels of interleukin (IL)1ß, IL6 and tumor necrosis factorα in vivo, and was demonstrated to promote chondrocyte injury and apoptosis by Safranin O staining and TUNEL. Moreover, the inhibition of miR3633p expression increased the expression of NRF1 and protected chondrocytes from apoptosis in vitro and in vivo, whereas the overexpression of miR3633p downregulated NRF1 expression and promoted LPSinduced chondrocyte apoptosis through the p53 pathway in vitro. The results of this study suggested that miR3633pmediated inhibition of NRF1may be associated with chondrocyte apoptosis in OA.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Transdução de Sinais
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Proteína Supressora de Tumor p53
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Apoptose
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MicroRNAs
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Fator 1 Relacionado a NF-E2
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article