The silencing of miR-199a-5p protects the articular cartilage through MAPK4 in osteoarthritis

Hanyu Lu; Yixin Yang; Shuanji Ou; Yong Qi; Guitao Li; Hebei He; Fanglian Lu; Wenjun Li; Hongtao Sun

doi:10.21037/atm-22-2057

The silencing of miR-199a-5p protects the articular cartilage through MAPK4 in osteoarthritis

Ann Transl Med. 2022 May;10(10):601. doi: 10.21037/atm-22-2057.

Authors

Hanyu Lu¹, Yixin Yang¹, Shuanji Ou¹, Yong Qi¹, Guitao Li¹, Hebei He¹, Fanglian Lu¹, Wenjun Li¹, Hongtao Sun¹

Affiliation

¹ Department of Orthopedics, Guangdong Second Provincial General Hospital, Guangzhou, China.

Abstract

Background: Osteoarthritis (OA) is the most common joint disorder, and places a heavy burden on individuals and society. As conventional therapies, such as surgery, rarely cure the disorder, targeted therapies represent a promising alternative. This research sought to explore the potential effect of miR-199a-5p on the development of OA.

Methods: Based on the OA rat model, the serum was collected at 6 and 12 weeks, and microRNA (miRNA) sequencing was performed. A bioinformatics analysis was conducted to examine the differentially expressed micro ribonucleic acids, and qRT-PCR (real-time quantitative PCR) was conducted to determine their expression in the joint tissues of rats with OA. Rats articular chondrocytes were collected and treated with a miR-199a-5p antagomir or agomir. Afterwards, cell viability, autophagy was determinated. Dual luciferase was used to verify that miR-199a-5p targets the regulation of mitogen-stimulated protein kinase 4 (MAPK4). Subsequently, in chondrocytes, MAPK was knockdown to rescue the effect of miR-199a-5p inhibition, and cell viability and autophagy were examined. Finally, the OA model was treated with miR-199a-5p antagomir to detect joint pathology, cartilage tissue and inflammatory factor and autophagy was measured.

Results: MiR-199a-5p was greatly upregulated in OA, and miRNA was found to be differentially expressed in OA tissues. MAPK4 was identified to be a target gene of miR-199-5p. Inhibiting miR-199a-5p not only decreased the survival of chondrocytes and induced apoptosis, but also relieved inflammation and decreased the content of pro-inflammatory cytokines. Further, the silencing of miR-199a-5p protected the articular cartilage and improved gait abnormalities, but this effect was abrogated by the silencing of MAPK4.

Conclusions: The silencing of miR-199a-5p appears to improve gait abnormalities, promote the survival of chondrocytes, and improve the condition of OA. Our findings may lead to the development of miR-199a-5p-based targeted therapy for OA.

Keywords: MAPK4; Osteoarthritis (OA); chondrocytes; miR-199a-5p.