Exosomal miRNA-128-3p from mesenchymal stem cells of aged rats regulates osteogenesis and bone fracture healing by targeting Smad5

Autor: Linwei Li, Guoyong Yin, Dingfei Qian, Jiaxing Wang, Tao Xu, Yongjun Luo, Ning Zhang, Changjiang Gu, Weihua Cai, Jin Fan
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Smad5 Protein
lcsh:Medical technology
lcsh:Biotechnology
Biomedical Engineering
Pharmaceutical Science
Medicine (miscellaneous)
Bioengineering
Bone healing
Mesenchymal Stem Cell Transplantation
Exosomes
Applied Microbiology and Biotechnology
Rats
Sprague-Dawley
Fractures
Bone
03 medical and health sciences
Paracrine signalling
chemistry.chemical_compound
0302 clinical medicine
Osteogenesis
In vivo
lcsh:TP248.13-248.65
medicine
Animals
Antagomir
030304 developmental biology
Fracture Healing
0303 health sciences
business.industry
Research
Mesenchymal stem cell
Cell Differentiation
Bone fracture
medicine.disease
Microvesicles
Rats
Transplantation
miR-128-3P
Disease Models
Animal
MicroRNAs
chemistry
lcsh:R855-855.5
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Mesenchymal stem cells
business
Smad5
Zdroj: Journal of Nanobiotechnology, Vol 18, Iss 1, Pp 1-18 (2020)
Journal of Nanobiotechnology
ISSN: 1477-3155
DOI: 10.1186/s12951-020-00601-w
Popis: Transplantation of mesenchymal stem cells (MSCs) has been considered an effective therapeutic treatment for a variety of diseases including bone fracture. However, there are associated complications along with MSCs transplantation. There is evidence to show that exosomes (Exos) derived from MSCs exert a similar paracrine function. In addition, repair capabilities of MSCs decline with age. Hence, this study aims to confirm whether the Exos protective function on osteogenic differentiation and fracture healing from aged MSCs was attenuated. This information was used in order to investigate the underlying mechanism. MSCs were successfully isolated and identified from young and aged rats, and Exos were then obtained. Aged-Exos exhibited significantly attenuated effects on MSCs osteogenic differentiation in vitro and facture healing in vivo. Using miRNA array analysis, it was shown that miR-128-3p was markedly upregulated in Aged-Exos. In vitro experiments confirmed that Smad5 is a direct downstream target of miR-128-3p, and was inhibited by overexpressed miR-128-3p. A series gain- and loss- function experiment indicated that miR-128-3P serves a suppressor role in the process of fracture healing. Furthermore, effects caused by miR-128-3P mimic/inhibitor were reversed by the application of Smad5/siSmad5. Taken together, these results suggest that the therapeutic effects of MSCs-derived Exos may vary according to differential expression of miRNAs. Exosomal miR-128-3P antagomir may act as a promising therapeutic strategy for bone fracture healing, especially for the elderly.
Databáze: OpenAIRE
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