Professor Huang Wei from the Department of Orthopaedics of the First Affiliated Hospital of Chongqing Medical University published an article titled “The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype” in Genes & Diseases (IF=7.243, Q1 ). 

The research result first proved that the alternative activated M2-Mφ apoptosis body can be induced by classical activation of M1-Mφ and phenotype transform to M2 reducing the progress of Osteoarthritis (OA), providing a new treatment strategy for various diseases related to the imbalance of inflammatory and anti-inflammatory immune responses. The fluorescence intensity was measured by an in vivo imaging system (AniView100, BLT, Guangzhou, China). The fluorescence intensity of tumor regions of interest was quantitatively analyzed using AniView software (BLT, Guangzhou, China)

Macrophages (Mφs) is a natural immune cell that can be polarized into classical activation (M1-Mϕs) by specific microenvironment signals and alternating activation (M2-Mϕs) two phenotypes exhibit pro-inflammatory and anti-inflammatory effects respectively. The balance between these two subtypes is crucial for the progression and prognosis of inflammatory diseases. Research has shown that in M1-Mϕ dominant, it will cause the occurrence and development of OA while promoting the inflammation of M1-Mφ. Reprogrammed as anti-inflammatory M2-Mφ, it can alleviate the synovitis and cartilage destruction of the OA model. The maintenance of macrophage phenotype is driven by genetic and epigenetic signals, as well as influenced by environmental signals, which provides a possible and effective treatment method for regulating macrophage polarization and preventing or treating osteoarthritis.

Apoptosis bodies (ABS) are products of programmed apoptosis that can be specifically recognized by macrophages through the "Eat-me" signal (calcium reticulin) on their surface. Previous studies have observed that phagocytosis of apoptotic cells (apoptosomes) by macrophages contributes to tissue repair and inflammation resolution.

It is unclear whether the reduction of inflammation and the enhancement of tissue repair is related to the phenotypic changes after macrophage uptake of apoptotic bodies, and further research is needed on the functions of apoptotic bodies.

Professor Huang Wei's team conducted the role of M2-Mϕs derived apoptotic bodies (M2-ABs) in regulating the M1/M2 balance of macrophages in an OA mouse model. Data shows that M2-ABS can be replaced by M1-Mϕ target uptake and reprogram M1 phenotype to M2 within 24 hours. M2-ABS significantly improved the severity of OA in mice, alleviated M1 mediated pro-inflammatory environment, and inhibited chondrocyte apoptosis. RNA-SEQ showed that M2-ABS is rich in miR-21-5p, which is a small RNA negatively associated with articular cartilage degeneration. The function of miR-21-5p significantly reduces the reprogramming of M1 towards M2 after in vitro cell transfection with M2-ABS.

△ Figure 1

Schematic illustration of apoptotic bodies-guided macrophage reprogramming. M2 M4-derived apoptotic bodies (M2-ABs) can trigger the switch of M1 to M2 M4s transformation and alleviate the progression of osteoarthritis

These results indicate that M2-derived M2 ABs can prevent joint cartilage damage and improve gait abnormalities in OA mice by reversing the inflammatory response induced by M1 macrophages. The mechanism may be related to the regulation and inhibition of inflammatory factors by miR-21-5p. The application of M2 ABs may represent a new cell therapy and may provide a valuable strategy for the treatment of OA or chronic inflammation.

△ Figure 2

In vivo biodistribution of M2-ABs.

Real-time in vivo imaging of Cy7 NHS labeled M2-ABs. The mice were analyzed at the indicated times after knee injection of phosphate-buffered saline (PBS) and 50 mg/ml of M2-ABs.

Ex vivo imaging of major organs at day 3 after mice had been treated with M2-ABs.

(C) Viscera distribution of fluorescent at day 3 after knee injection of Cy7-NHS labeled M2-ABs.

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Reference：

Leilei Qin, Jianye Yang, Xudong Su,Xilan li, Yiting Lei, Lili Dong, Hong Chen, Cheng Chen, Chen Zhao, Huan Zhang, Jun Deng, Ning Hu, Wei Huang,The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype, Genes & Diseases,

Volume 10, Issue 3,2023, Pages 1114-1129,ISSN 2352 3042, https://doi.org/10.1016/j.gendis.2022.09.010