MicroRNA‑1 regulates the development of osteoarthritis in a Col2a1‑Cre‑ERT2/GFPfl/fl‑RFP‑miR‑1 mouse model of osteoarthritis through the downregulation of Indian hedgehog expression

Abstract

The present study assessed the effects of microRNA-1 (miR-1) on the development of osteoarthritis using human tissues and a col2a1-cre-ER T2 /GFP fl/fl-RFP-miR-1 mouse model of osteoarthritis. Human cartilage tissues (n=20) were collected for reverse transcription-quantitative polymerase chain reaction (RT-qPcR), histological analysis and immunohistochemistry experiments. A transgenic mouse model of osteoarthritis was established by subjecting col2a1-cre-ER T2 /GFP fl/fl-RFP-miR-1 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, RT-qPcR and Safranin O staining. It was found that the miR-1 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 miR-1, as well as collagen, type II (col2a1) and Aggrecan (Acan) expression; however, it decreased Ihh, glioma-associated 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 non-tamoxifen + 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 MMP-13 was significantly higher in the joint tissues of the non-tamoxifen + AcLT group than in those of the tamoxifen + AcLT group. However, col2a1 expression was lower in the joint tissues of the non-tamoxifen + AcLT group than in those of the tamoxifen + AcLT group. The results of RT-qPcR and FMT further confirmed these findings. On the whole, the findings of the present study demonstrate that miR-1 expression protects against osteoarthritis-induced cartilage damage and gene expression by inhibiting Ihh signaling.

Downregulation of miR-1-3p expression inhibits the hypertrophy and mineralization of chondrocytes in DDH

“…To further elucidate the role of other miRNAs in DDH pathogenesis, we performed qPCR verification and discovered very low expression of miR-1-3p, which was in accordance with our previous miRNA chip data [ 13 ]. It has been reported that miR-1-3p expression is downregulated in osteoarthritic cartilage and confirmed that miR-1-3p is closely related to osteoarthritis [ 21 ]. However, the role of miRNA in DDH is unknown.…”

Bioinformatics-Led Discovery of Osteoarthritis Biomarkers and Inflammatory Infiltrates

“…It is the major cause of disability and is characterized by cartilage destruction and bone fragmentation in joints ( 2 , 3 ). Prior joint injury, abnormal joint or limb development, genetic background, and having a job that requires heavy lifting are among the risk factors for osteoarthritis caused by mechanical stress on the joints and low levels of inflammation ( 4 ). osteoarthritis is the most common chronic joint disease, which cannot be prevented, and its prevalence rises with age ( 5 – 7 ).…”

Single-cell RNA sequencing analysis reveals the relationship of bone marrow and osteopenia in STZ-induced type 1 diabetic mice

“…X-ray radiography was performed using a small-animal X-ray apparatus (UltraFocus, Faxitron) to detect the difference in BMD changes in group C(n = 6) and D(n = 5) mice’s left legs. The exposure time and kV were set to the auto setting [29] . The window level was set from 2058 to 7200.…”