MicroRNA-132 upregulation promotes matrix degradation in intervertebral disc degeneration.
Exp Cell Res
; 359(1): 39-49, 2017 10 01.
Article
en En
| MEDLINE
| ID: mdl-28793234
ABSTRACT
MicroRNAs (miRNAs) have been shown to be involved in the pathogenesis of intervertebral disc degeneration (IDD). This experiment was designed to study the expression and role of the miRNA, miR-132, in IDD. MiR-132 expression in human nucleus pulposus (NP) tissue was assessed by quantitative real-time PCR. The methylation status of the miR-132 was assessed with methylation-specific PCR and bisulfite sequencing PCR. The regulation of growth differentiation factor5 (GDF5) expression by miR-132 was evaluated by luciferase reporter assay. Moreover, we investigated the function of miR-132 on IDD in vivo using a classic needle-punctured rat tail model. These results showed that miR-132 expression was upregulated during IDD and this upregulation was associated with hypomethylation of its promoter. MiR-132 overexpression led to increased expression of ECM catabolic factors, including MMP13 and ADAMTS4, in NP cells while levels of anabolic proteins, such as type II collagen and aggrecan, were diminished. GDF5 was identified as a direct target of negative regulation by miR-132. MAPK/ERK signaling was also found to be associated with miR-132-induced ECM degradation. In addition, we showed that miR-132 inhibition effectively attenuated NP ECM degradation in IDD in vivo. Our findings demonstrated that miR-132 promotes ECM degradation by human NP cells by direct targeting of GDF5. Hence, miR-132 represents a potential therapeutic target in the treatment of IDD.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Regulación hacia Arriba
/
MicroARNs
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Matriz Extracelular
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Degeneración del Disco Intervertebral
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Exp Cell Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
China