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Stem Cell Res Ther. 2019 Jun 18;10(1):180. doi: 10.1186/s13287-019-1285-y.

miR-34a promotes bone regeneration in irradiated bone defects by enhancing osteoblastic differentiation of mesenchymal stromal cells in rats.

Author information

1
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, China.
2
Xi'an Institute of Tissue Engineering and Regenerative Medicine, No. 169 West Changle Road, Xi'an, 710032, China.
3
Department of Stomatology, The 7th Medical Center of PLA General Hospital, NO.5, Nanmencang, Dongsishitiao Street, Beijing, 100700, China.
4
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, China. zhaoymdentist@126.com.

Abstract

BACKGROUND:

Radiation exposure negatively affects the regenerative ability and makes reconstruction of bone defects after tumor section difficult. miR-34a is involved in radiation biology and bone metabolism. The aim of this study was to investigate whether miR-34a could contribute to bone regeneration in irradiated bone defects.

METHODS:

The expression of miR-34a was analyzed during the osteoblastic differentiation of irradiated BMSCs and bone formation in irradiated bone defects. miR-34a mimics and miR-34a inhibitor were used to upregulate or suppress the expression of miR-34a in BMSCs irradiated with 2 or 4 Gy X-ray radiation. In vitro osteogenesis and subcutaneous osteogenesis were used to assess the effects of miR-34a on the osteogenic ability of radiation-impaired BMSCs. Collagen-based hydrogel containing agomiR-34a or antagomiR-34a were placed into the 3-mm defects of irradiated rat tibias to test the effect of miR-34a on bone defect healing after irradiation.

RESULTS:

miR-34a was upregulated in the process of bone formation after irradiation. Transfecting radiation-impaired BMSCs with miR-34a mimics enhanced their osteoblastic differentiation in vitro by targeting NOTCH1. Overexpression of miR-34a enhanced the ectopic bone formation of irradiated BMSCs. In situ delivery of miR-34a promoted bone regeneration in irradiated bone defects.

CONCLUSIONS:

miR-34a promoted the osteoblastic differentiation of BMSCs and enhanced the ectopic bone formation after irradiation. miR-34a promoted bone defect healing in irradiated rat tibias. miR-34a-targeted therapy might be a promising strategy for promoting the reconstruction of bone defects after radiotherapy.

KEYWORDS:

Bone marrow mesenchymal stromal cell; Bone regeneration; Osteoblastic differentiation; Radiotherapy; miR-34a

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