MicroRNA-4287 alleviates inflammatory response via targeting RIPK1 in osteoarthritis

Abstract

Studies have confirmed the regulatory effects of microRNAs (miRNAs) in osteoarthritis (OA) progression. MiR-4287 has been identified by a previous study as a downregulated miRNA in chondrocytes treated with IL-1β and TNF-α. However, the function of the underlying mechanism of miR-4287 in OA is elusive. IL-1β-treated chondrocytes were used as OA cell models. RNA expression was accessed using RT-qPCR. Cell Counting Kit-8 (CCK-8) assay was used to determine the chondrocytes' viability and proliferation. The protein levels of inflammation factors (IL-8, IL-6, and TNF-α), matrix metalloproteinases (MMP 1, MMP3, MMP13), and chondrogenic genes (COL2A1, SOX9, and Aggrecan) were detected using western blot analysis. Luciferase reporter assays were performed for interaction exploration. HE staining and Safranin O/Fast Green staining was used to access the pathological changes in OA mouse tissues and cartilage degeneration in OA mouse. MiR-4287 was downregulated in chondrocytes treated with IL-1β and OA mouse models. MiR-4287 overexpression promoted the viability, and proliferation and attenuated the inflammation response and destruction of cartilage in IL-1β-stimulated chondrocytes. Receptor-interacting protein kinase 1 (RIPK1) was a target gene of miR-4287 in chondrocytes. MiR-4287 negatively regulated RIPK1 expression. RIPK1 overexpression was revealed to reverse the miR-4287-mediated effects on proliferation and inflammatory response in IL-1β-stimulated chondrocytes. Moreover, miR-4287 was demonstrated to inhibit the pathological changes, cartilage degeneration and inflammation response in OA mice models. In conclusion, miR-4287 is a critical molecule in OA development, which attenuates inflammatory response in vivo and in vitro by targeting RIPK1.

Keywords:

• miR-4287
• RIPK1
• osteoarthritis

Disclosure statement

Mingyang Xia declares that she has no conflict of interest. Jiajun Lu declares that she has no conflict of interest. Yixiong Wu declares that she has no conflict of interest. Xiaoguang Feng declares that she has no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.