miRNA-29b improves bone healing in mouse fracture model.
A number of miRNAs regulates bone remodeling and their levels in circulation were associated with bone fracture, however no miRNAs have yet been shown to improve fracture healing directly. This study aimed to investigate the effect of miR-29b-3p on mice femoral fracture healing through site-specific delivery with microbubble-ultrasound system. miR-29b-3p promoted osteogenesis of mouse bone marrow-derived mesenchymal stem cells as indicated with quantitative real-time polymerase chain reaction (qPCR) and Alizarin red S staining. Animal study showed that single injection of miR-29b-3p at week 2 post fracture improved healing outcome as indicated by significant decrease of callus width and area with radiographic analysis without causing significant weight loss. Static bone histomorphometry analysis showed that miR-29b-3p increased bone volume fraction (BV/TV), and micro-computed tomography (micro-CT) measurement showed increased BV/TV of high density bone and bone mineral density (BMD) of the callus. 3 point bending mechanical test showed improved relative stiffness. However, repeated injection of miR-29b-3p at weeks 2 and 3 did not result in additive therapeutic outcome, and caused increased total tissue volume and reduced BMD of the callus. This is the first report showing significant therapeutic effect of miR-29b-3p on femoral fracture healing through site-specific delivery with microbubble-ultrasound system. Further studies are warranted to investigate the underlying mechanisms and to refine the treatment protocol.
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; SMART Program, Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: waynelee@ort.cuhk.edu.hk.
Wayne Y
WY
Lee
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Nan
N
Li
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; SMART Program, Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Sien
S
Lin
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; SMART Program, Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Bin
B
Wang
Department of Medicine and Therapeutics, Faculty of Medicine, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Hui Y
HY
Lan
Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; SMART Program, Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Gang
G
Li
D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D017102:Fracture Healing / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D045423:Microbubbles; D010012:Osteogenesis / Q000235:genetics; D010957:Plasmids / Q000378:metabolism; D014162:Transfection; D014465:Ultrasonics; D055114:X-Ray Microtomography
C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs
Bone healing; Microbubble-ultrasound system; Mouse fracture; miR-29b-3p