RETRACTED ARTICLE: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3

Abstract

Background: Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo, and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation. Results: We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 (SIK2 and SIK3) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo. Conclusions: Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.

Communications Between Bone Marrow Macrophages and Bone Cells in Bone Remodeling

“…Macrophages can produce TGF-β1, which is essential for bone metabolism. NF-kB, composed of subunits such as p65, is a downstream transcription factor of the RANKL-RANKL signaling pathway (Park et al, Interfere the PTEN/PI3K/AKT signaling pathway to regulate the biological behavior of cells Zheng et al, 2017;Yang et al, 2018 mir-155 Promote the secretion of inflammatory cytokines Stanczyk et al, 2008;Heymans et al, 2013;Ying et al, 2017 mir-5106 Inhibit the genes SIK2 and SIK3 to promote bone formation Xiong et al, 2020 Alarmins Annexins Induce bone resorption and help macrophages to work Li et al, 2005;D'Souza et al, 2012;Stukes et al, 2016;McArthur et al, 2020;Xia et al, 2020;Xiong et al, 2020 Galectins Act on the differentiation of various bone cells Andersen et al, 2003;Shimura et al, 2005;Nakajima et al, 2014;Weilner et al, 2016;Simon et al, 2017;Iacobini et al, 2018 HSP; fibronectin Functions through osteoblasts and osteoclasts. Moursi et al, 1996;Koh et al, 2009;Gramoun et al, 2010;Notsu et al, 2016;Nakamura et al, 2019 2017).…”

“…The latest studies found that M2-type macrophages derived from mouse bone marrow macrophages enriched miR-5106. M2D-Exo containing miR-5106 can promote osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate fracture healing in vivo by inhibiting the expression of osteogenic related genes SIK2 and SIK3 ( Figure 3 ) (Xiong et al, 2020 ). Unexpectedly, compared to exosomes from M0 and M2, exosomes from M1 have a stronger stimulating effect on the proliferation, osteogenesis, and adipogenic differentiation of BMSCS and all three types of exosomes had an adverse effect on the chondrogenic differentiation of BMMSCs (Xia et al, 2020 ).…”

Exosomes: A Friend or Foe for Osteoporotic Fracture?

“…Interestingly, using bioinformatics analysis and related assays, they further found that high-fat treatment could decrease the secretion of BM-MSCs-derived exosomes and reduce the carried lncRNA H19 via miR-467/HoxA10 axis, hence affecting osteogenic differentiation and fracture (96). Liu et al performed a serious of in vivo and (98).…”

Correction to: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3

“…Following publication of the original article [ 1 ], the authors reported that Fig. 2 was not updated during the production process.…”