M2 macrophage-derived exosomes carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-β1

被引:4
|
作者
Huang, Chong [1 ]
Zhao, Lu [2 ]
Xiao, Yun [3 ]
Tang, Zihao [2 ]
Jing, Li [2 ]
Guo, Kai [2 ]
Tian, Lei [2 ]
Zong, Chunlin [2 ]
机构
[1] Northwest Univ, Coll Life Sci, Key Lab Biotechnol Shaanxi Prov, 229 Taibai North Rd, Xian 710069, Peoples R China
[2] Fourth Mil Med Univ, Natl Clin Res Ctr Oral Dis, Shaanxi Clin Res Ctr Oral Dis, Sch Stomatol,Dept Oral & Maxillofacial Surg,State, 145 West Changle Rd, Xian 710032, Peoples R China
[3] Jiamusi Univ, Sch Stomatol, 522 Hongqi St, Jiamusi 154000, Peoples R China
基金
中国国家自然科学基金;
关键词
Bone marrow mesenchymal stem cells; Macrophages; Exosomes; miRNAs; Irradiation-induced bone damage; MESENCHYMAL STEM-CELLS; OSTEOGENIC DIFFERENTIATION; BONE; RADIATION; INJURY; FIBROSIS;
D O I
10.1007/s11010-023-04775-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Radiotherapy is essential to cancer treatment, while it inevitably injures surrounding normal tissues, and bone tissue is one of the most common sites prone to irradiation. Bone marrow mesenchymal stem cells (BMMSCs) are sensitive to irradiation and the irradiated dysfunction of BMMSCs may be closely related to irradiation-induced bone damage. Macropahges play important role in regulating stem cell function, bone metabolic balance and irradiation response, but the effects of macrophages on irradiated BMMSCs are still unclear. This study aimed to investigate the role of macrophages and macrophage-derived exosomes in restoring irradiated BMMSCs function. The effects of macrophage conditioned medium (CM) and macrophage-derived exosomes on osteogenic and fibrogenic differentiation capacities of irradiated BMMSCs were detected. The key microribonucleic acids (miRNAs) and targeted proteins in exosomes were also determined. The results showed that irradiation significantly inhibited the proliferation of BMMSCs, and caused differentiation imbalance of BMMSCs, with decreased osteogenic differentiation and increased fibrogenic differentiation. M2 macrophage-derived exosomes (M2D-exos) inhibited the fibrogenic differentiation and promoted the osteogenic differentiation of irradiated BMMSCs. We identified that miR-142-3p was significantly overexpressed in M2D-exos and irradiated BMMSCs treated with M2D-exos. After inhibition of miR-142-3p in M2 macrophage, the effects of M2D-exos on irradiated BMMSCs differentiation were eliminated. Furthermore, transforming growth factor beta 1 (TGF-beta 1), as a direct target of miR-142-3p, was significantly decreased in irradiated BMMSCs treated with M2D-exos. This study indicated that M2D-exos could carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-beta 1. These findings pave a new way for promising and cell-free method to treat irradiation-induced bone damage.
引用
收藏
页码:993 / 1010
页数:18
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