Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance

Diabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear. We isolated exosomes secreted by bone mar...

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Bibliographic Details
Published in:Frontiers in endocrinology (Lausanne) 2023-04, Vol.14, p.1149168-1149168
Main Authors: Han, Fei, Wang, Chao, Cheng, Peng, Liu, Ting, Wang, Wei-Shan
Format: Article
Language:English
Subjects:
Animals
Bone and Bones - metabolism
bone-fat imbalance
diabetes
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - genetics
Diabetes Mellitus, Experimental - metabolism
Endocrinology
exosomes
Mesenchymal Stem Cells - metabolism
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
miR-221
Osteogenesis - genetics
osteoporosis
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Summary:Diabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear. We isolated exosomes secreted by bone marrow mesenchymal stem cells of normal and diabetic mice and test their effects on osteogenesis and adipogenesis. Then we screened the differential microRNAs by high-throughput sequencing and explored the function of key microRNA and . We find that lower bone mass and higher marrow fat accumulation, also called bone-fat imbalance, exists in diabetic mouse model. Exosomes secreted by normal bone marrow mesenchymal stem cells (BMSCs-Exos) enhanced osteogenesis and suppressed adipogenesis, while these effects were diminished in diabetic BMSCs-Exos. miR-221, as one of the highly expressed miRNAs within diabetic BMSCs-Exos, showed abilities of suppressing osteogenesis and promoting adipogenesis both and . Elevation of miR-221 level in normal BMSCs-Exos impairs the ability of regulating osteogenesis and adipogenesis. Intriguingly, using the aptamer delivery system, delivery normal BMSCs-Exos specifically to BMSCs increased bone mass, reduced marrow fat accumulation, and promoted bone regeneration in diabetic mice. We demonstrate that BMSCs derived exosomal miR-221 is a key regulator of diabetic osteoporosis, which may represent a potential therapeutic target for diabetes-related skeletal disorders.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2023.1149168