MicroRNA1 regulates the development of osteoarthritis in a Col2a1CreERT2/GFPfl/flRFPmiR1 mouse model of osteoarthritis through the downregulation of Indian hedgehog expression.
Int J Mol Med
; 46(1): 360-370, 2020 Jul.
Article
en En
| MEDLINE
| ID: mdl-32626917
ABSTRACT
The present study assessed the effects of microRNA1 (miR1) on the development of osteoarthritis using human tissues and a Col2a1CreERT2/GFPfl/flRFPmiR1 mouse model of osteoarthritis. Human cartilage tissues (n=20) were collected for reverse transcriptionquantitative polymerase chain reaction (RTqPCR), histological analysis and immunohistochemistry experiments. A transgenic mouse model of osteoarthritis was established by subjecting Col2a1CreERT2/GFPfl/flRFPmiR1 transgenic mice to anterior cruciate ligament transection (ACLT). Mice were subjected to radiography and in vivo fluorescence molecular tomography (FMT), while mouse tissues were collected for histological analysis, RTqPCR and Safranin O staining. It was found that the miR1 level was downregulated, whereas the levels of Indian hedgehog (Ihh), as well as those of its downstream genes were upregulated in human osteoarthritic cartilage. In the transgenic mice, treatment with tamoxifen induced miR1, as well as collagen, type II (Col2a1) and Aggrecan (Acan) expression; however, it decreased Ihh, gliomaassociated oncogene homolog (Gli)1, Gli2, Gli3, smoothened homolog (Smo), matrix metalloproteinase (MMP)13 and collagen type X (Col10) expression. Safranin O staining revealed cartilage surface damage in the nontamoxifen + ACLT group, compared with that in the tamoxifen + ACLT group. Histologically, an intact cartilage surface and less fibrosis were observed in the tamoxifen + ACLT group. Immunohistochemistry revealed that the protein expression of Ihh, Col10, and MMP13 was significantly higher in the joint tissues of the nontamoxifen + ACLT group than in those of the tamoxifen + ACLT group. However, Col2a1 expression was lower in the joint tissues of the nontamoxifen + ACLT group than in those of the tamoxifen + ACLT group. The results of RTqPCR and FMT further confirmed these findings. On the whole, the findings of the present study demonstrate that miR1 expression protects against osteoarthritisinduced cartilage damage and gene expression by inhibiting Ihh signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoartritis
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Colágeno Tipo II
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MicroARNs
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Proteínas Hedgehog
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article