MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression.
Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfully established the DO model of rats, a microRNA microarray was performed to find molecular targets for DO. Total 100 microRNAs were identified as differently expressed, with miR-503 being one of the most significantly up-regulated miRNAs in DO. The further investigation also showed that miR-503 was upregulated during osteogenesis in mesenchymal stem cells of rats, and overexpression of miR-503 significantly promoted osteogenesis in vitro and accelerated mineralization in DO process in vivo. By using bioinformatic investigations and luciferase activities, we successfully demonstrated that Smurf1, a negative regulator of osteogenesis, was a real target of miR-503. Furthermore, Smurf1 knockdown promoted osteogenesis and antagomir-503 abolished the promotive effect, suggesting that miR-503 mediated osteogenic differentiation via suppressing Smurf1 expression. To sum up, these findings indicated that miR-503 promoted osteogenesis and accelerated bone formation, which may shed light on the development for a potential therapeutic target for bone repair.
Department of Orthopaedics and Traumatology, Bao-An District People's Hospital, Shenzhen, P.R. China.|Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, P.R. China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China.
Yuxin
Y
Sun
Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.
Jia
J
Xu
Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, P.R. China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China.
Liangliang
L
Xu
Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, P.R. China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China.
Jinfang
J
Zhang
Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, P.R. China.
Kaiming
K
Chan
Department of Orthopaedics and Traumatology, Bao-An District People's Hospital, Shenzhen, P.R. China. 568282414@qq.com.
Xiaohua
X
Pan
Department of Orthopaedics and Traumatology, Bao-An District People's Hospital, Shenzhen, P.R. China. gangli@cuhk.edu.hk.|Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences and Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, P.R. China. gangli@cuhk.edu.hk.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, P.R. China. gangli@cuhk.edu.hk.|Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China. gangli@cuhk.edu.hk.
Gang
G
Li
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D010012:Osteogenesis; D019857:Osteogenesis, Distraction; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation
C571410:MIRN503 microRNA, rat; D035683:MicroRNAs; C556581:Smurf1 protein, rat; D044767:Ubiquitin-Protein Ligases