Exosomes Derived from M2 Macrophages Exert a Therapeutic Effect via Inhibition of the PI3K/AKT/mTOR Pathway in Rats with Knee Osteoarthritic.

Zha Xi Da-Wa,Wei Shu-Qing,Li De-Chun,Lu Chuan,Dong Zu-Nan,Ma Jun,Li Ke-Wen,Yang Sen-Lin,Liu Chao-Zheng,Zhao Hong-Tao,Pei Xian-Wei,Liu Wenbo,Rui Liu

doi:10.1155/2021/7218067

Abstract

Macrophages are commonly classified as M1 macrophages or M2 macrophages. M2 macrophages are obtained by stimulation of IL-4 with anti-inflammatory and tissue repair effects. Exosomes are 30–150 nm lipid bilayer membrane vesicles derived from most living cells and have a variety of biological functions. Previous studies have shown that macrophage exosomes can influence the course of some autoimmune diseases, but their effect on knee osteoarthritis (KOA) has not been reported. Here, we analyze the roles of exosomes derived from M2 macrophage phenotypes in KOA rats. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), Western blotting, and DLS. The results showed that M2 macrophage exosomes significantly attenuated the inflammatory response and pathological damage of articular cartilage in KOA rats. In addition, a key protein associated with KOA including Aggrecan, Col-10, SOX6, and Runx2 was significantly increased, while MMP-13 was significantly suppressed following treatment with M2 macrophage exosomes. The present study indicated that M2 macrophage exosomes exerted protective effects on KOA rats mainly mediated by the PI3K/AKT/mTOR signal pathway. These findings provide a novel approach for the treatment of KOA.

Highlights

Knee osteoarthritis (KOA) is a degenerative disease with the main symptoms of knee joint pain and swelling, severely affected and accompanied by joint deformities [1]
Bone marrow-derived monocytes were isolated from mouse femurs and tibias and were polarized by M-CSF to M0-macrophages, followed by IL-4 to M2 macrophages
The above experimental results showed that M2 macrophages were successfully polarized and could be used for exosome isolation

Summary

Introduction

Knee osteoarthritis (KOA) is a degenerative disease with the main symptoms of knee joint pain and swelling, severely affected and accompanied by joint deformities [1]. Due to changes in people’s dietary structure and increasing social aging, the incidence of osteoarthritis is increasing year by year [2]. Epidemiological investigations show that the incidence of osteoarthritis is about 40.2% [3]. The most common treatment methods for osteoarthritis include physical therapy, drug therapy, surgical treatment, and traditional Chinese medicine treatment [4]. There are side effects of medications prescribed in medicine and injury of surgical treatment. There is an urgent need for new strategies to suppress the inflammatory effect and alleviate KOA

Results

Discussion

Conclusion