Inhibition of miR‐92a Enhances Fracture Healing via Promoting Angiogenesis in a Model of Stabilized Fracture in Young Mice |
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| Authors: | Koichi Murata Hiromu Ito Hiroyuki Yoshitomi Koji Yamamoto Akinobu Fukuda Junsuke Yoshikawa Moritoshi Furu Masahiro Ishikawa Hideyuki Shibuya Shuichi Matsuda |
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| Affiliation: | 1. Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan;2. Department of the Control for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan;3. Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan;4. Department of Orthopaedic Surgery, Yoshikawa Hospital, Kyoto, Japan |
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| Abstract: | ![]()
MicroRNAs (miRNAs) are endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes. Although no miRNA has been reported to play an important role in the regulation of fracture healing, several miRNAs control key elements in tissue repair processes such as inflammation, hypoxia response, angiogenesis, stem cell differentiation, osteogenesis, and chondrogenesis. We compared the plasma concentrations of 134 miRNAs in 4 patients with trochanteric fractures and 4 healthy controls (HCs), and the levels of six miRNAs were dysregulated. Among these miRNAs, miR‐92a levels were significantly decreased 24 hours after fracture, compared to HCs. In patients with a trochanteric fracture or a lumbar compression fracture, the plasma concentrations of miR‐92a were lower on days 7 and 14, but had recovered on day 21 after the surgery or injury. To determine whether systemic downregulation of miR‐92a can modulate fracture healing, we administered antimir‐92a, designed using locked nucleic acid technology to inhibit miR‐92a, to mice with a femoral fracture. Systemic administration of antimir‐92a twice a week increased the callus volume and enhanced fracture healing. Enhancement of fracture healing was also observed after local administration of antimir‐92a. Neovascularization was increased in mice treated with antimir‐92a. These results suggest that plasma miR‐92a plays a crucial role in bone fracture healing in human and that inhibition of miR‐92a enhances fracture healing through angiogenesis and has therapeutic potential for bone repair. © 2014 American Society for Bone and Mineral Research. |
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| Keywords: | MICRORNA FRACTURE HEALING ANGIOGENESIS LOCKED NUCLEIC ACID BIOMARKER |
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