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

• Main Authors: Huan Liu, Yan Dong, Xiaoke Feng, Liya Li, Yang Jiao, Shizhu Bai, Zhihong Feng, Hao Yu, Xuejian Li, Yimin Zhao
• Format: Article
• Language: English
• Published: BMC 2019-06-01
• Series: Stem Cell Research & Therapy
• Subjects: miR-34a; Bone marrow mesenchymal stromal cell; Bone regeneration; Osteoblastic differentiation; Radiotherapy
• Online Access: http://link.springer.com/article/10.1186/s13287-019-1285-y
• ISSN: 1757-6512

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.