miR-7/EGFR/MEGF9 axis regulates cartilage degradation in osteoarthritis via PI3K/AKT/mTOR signaling pathway

• Published in: Bioengineered Vol. 12; no. 1; pp. 8622 - 8634
• Main Authors: Jiang, Lifeng, Zhou, Xindie, Xu, Kai, Hu, Pengfei, Bao, Jiapeng, Li, Jin, Zhu, Junfeng, Wu, Lidong
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2021
• Subjects: Animals; Cartilage - cytology; Cartilage - metabolism; Cartilage - pathology; cartilage degradation; Cells, Cultured; Chondrocytes - metabolism; EGFR; ErbB Receptors - genetics; ErbB Receptors - metabolism; Humans; Male; MEGF9; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miR-7; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Osteoarthritis; Osteoarthritis - metabolism; Osteoarthritis - pathology; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Research Paper; Signal Transduction - genetics; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; miR-7; cartilage degradation; Osteoarthritis; EGFR; MEGF9
• ISSN: 2165-5979; 2165-5987; 2165-5987
• DOI: 10.1080/21655979.2021.1988362

Osteoarthritis (OA) is a common degenerative disease in middle-aged and elderly people. Our previous study has proved that microRNA-7 (miR-7) exacerbated the OA process. This study was aimed to explore the downstream genes and mechanism regulated by miR-7 to affect OA. Multiple EGF-like-domains 9 (MEGF9) was the predicted target of miR-7 by databases. Luciferase report experiment results confirmed that MEGF9 could bind to miR-7. Among the 10 collected pairs of OA and healthy samples, the expression levels of miR-7 and MEGF9 were both up-regulated when compared with healthy subjects by qRT-PCR and immunohistochemistry (IHC). The increased MEGF9 levels were due to the interaction with epidermal growth factor receptor (EGFR) by co-immunoprecipitation. Evaluations found that upregulation of miR-7 or MEGF9 can increase the expression of EGFR, matrix metalloproteinase-13 (MMP-13) and a disintegrin like and metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS-5), so as to aggravate cartilage degradation. In addition, this effect induced by miR-7/EGFR/MEGF9 axis was by activation of PI3K/AKT signaling. The IHC and western blot assay results on OA model mice also demonstrated that miR-7/EGFR/MEGF9 axis regulated cartilage degradation in vivo. In summary, miR-7/EGFR/MEGF9 axis may perform a crucial function in the regulation of OA, providing potential for OA treatment.