Macrophage-derived extracellular vesicles regulate skeletal stem/ progenitor Cell lineage fate and bone deterioration in obesity

被引:0
作者
He, Chen [1 ]
Hu, Chen [1 ]
He, Wen-Zhen [1 ]
Sun, Yu-Chen [1 ]
Jiang, Yangzi [2 ,3 ,4 ]
Liu, Ling [1 ]
Hou, Jing [1 ]
Chen, Kai-Xuan [1 ]
Jiao, Yu-Rui [1 ]
Huang, Mei [1 ]
Huang, Min [1 ]
Yang, Mi [1 ]
Lu, Qiong [5 ]
Wei, Jie [6 ,7 ,8 ,10 ]
Zeng, Chao [6 ,7 ,8 ,9 ,10 ]
Lei, Guang-Hua [6 ,8 ,9 ,10 ]
Li, Chang-Jun [1 ,9 ,10 ]
机构
[1] Cent South Univ, Endocrinol Res Ctr, Dept Endocrinol, Xiangya Hosp, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
[2] Chinese Univ Hong Kong, Inst Tissue Engn & Regenerat Med, Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Ctr Neuromusculoskeletal Restorat Med CNRM, Hong Kong, Peoples R China
[4] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med,Minist Educ, Hong Kong, Peoples R China
[5] Cent South Univ, Dept Pharm, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China
[6] Cent South Univ, Dept Orthopaed, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China
[7] Cent South Univ, Xiangya Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Changsha 410008, Hunan, Peoples R China
[8] Hunan Key Lab Joint Degenerat & Injury, Changsha 410008, Hunan, Peoples R China
[9] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
[10] Cent South Univ, Xiangya Hosp, Key Lab Aging related Bone & Joint Dis Prevent & T, Minist Educ, Changsha, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
Obesity-induced bone deterioration; Macrophage-derived extracellular vesicles; Skeletal stem/progenitor cells; Cell fate; Aptamer; Cell-specific targeting; ADIPOSE-TISSUE; MARROW; OSTEOGENESIS; PATHWAY; MICE;
D O I
10.1016/j.bioactmat.2024.06.035
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Ppar alpha-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.
引用
收藏
页码:508 / 523
页数:16
相关论文
共 21 条
[21]   CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis [J].
Shi, Zuowei ;
Wang, Kaifu ;
Xing, Yufei ;
Yang, Xuefeng .
FRONTIERS IN ONCOLOGY, 2021, 11