Increased microRNA-93-5p inhibits osteogenic differentiation by targeting bone morphogenetic protein-2

• Published in: PloS one Vol. 12; no. 8; p. e0182678
• Main Authors: Zhang, Ying, Wei, Qiu-Shi, Ding, Wei-Bin, Zhang, Lei-Lei, Wang, Hui-Chao, Zhu, Ying-Jie, He, Wei, Chai, Yu-Na, Liu, You-Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.08.2017; Public Library of Science (PLoS)
• Subjects: Abnormalities, Multiple; Adult; Alkaline phosphatase; Base Sequence; Binding Sites; Biocompatibility; Bioinformatics; Biology and life sciences; Bone marrow; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Bone morphogenetic proteins; Bone turnover; Cancer; Cell culture; Cell cycle; Cell growth; Collapse; Comparative analysis; Computed tomography; Degeneration; Destruction; Differentiation; Disease; DNA microarrays; Female; Femoral Neck Fractures - complications; Femoral Neck Fractures - metabolism; Femoral Neck Fractures - pathology; Femur; Femur Head Necrosis - etiology; Femur Head Necrosis - metabolism; Femur Head Necrosis - pathology; Fractures; Gangrene; Gene expression; Genetic aspects; Head; HEK293 Cells; Hip; Hip joint; Homeostasis; Hospitals; Humans; Immunohistochemistry; Joint surgery; Limb Deformities, Congenital; Male; Mandibulofacial Dysostosis; Medicine and Health Sciences; Mesenchyme; Metabolism; Micrognathism; MicroRNA; MicroRNAs; MicroRNAs - physiology; Middle Aged; miRNA; Necrosis; Osteoblasts - physiology; Osteogenesis; Osteonecrosis; Osteopontin; Pain; Patients; Physiological aspects; Polymerase chain reaction; Proteins; Ribonucleic acid; RNA; RNA Interference; Sequence Analysis, DNA; Signal transduction; Stem cells; Subchondral bone; Surgical implants; Transcription factors; Trauma; Young Adult; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182678

Trauma-induced osteonecrosis of the femoral head (TIONFH) is a major complication of femoral neck fractures. Degeneration and necrosis of subchondral bone can cause collapse, which results in hip joint dysfunction in patients. The destruction of bone metabolism homeostasis is an important factor for osteonecrosis. MicroRNAs (miRNAs) have an important role in regulating osteogenic differentiation, but the mechanisms underlying abnormal bone metabolism of TIONFH are poorly understood. In this study, we screened specific miRNAs in TIONFH by microarray and further explored the mechanism of osteogenic differentiation. Blood samples from patients with TIONFH and patients without necrosis after trauma were compared by microarray, and bone collapse of necrotic bone tissue was evaluated by micro-CT and immunohistochemistry. To confirm the relationship between miRNA and osteogenic differentiation, we conducted cell culture experiments. We found that many miRNAs were significantly different, including miR-93-5p; the increase in this miRNA was verified by Q-PCR. Comparison of the tissue samples showed that miR-93-5p expression increased, and alkaline phosphatase (ALP) and osteopontin (OPN) levels decreased, suggesting miR-93-5p may be involved in osteogenic differentiation. Further bioinformatics analysis indicated that miR-93-5p can target bone morphogenetic protein 2 (BMP-2). A luciferase gene reporter assay was performed to confirm these findings. By simulating and/or inhibiting miR-93-5p expression in human bone marrow mesenchymal stem cells, we confirmed that osteogenic differentiation-related indictors, including BMP-2, Osterix, Runt-related transcription factor, ALP and OPN, were decreased by miR-93-5p. Our study showed that increased miR-93-5p in TIONFH patients inhibited osteogenic differentiation, which may be associated with BMP-2 reduction. Therefore, miR-93-5p may be a potential target for prevention of TIONFH.