MiR-181a-5p promotes osteogenesis by targeting BMP3

• Published in: Aging (Albany, NY.) Vol. 15; no. 3; pp. 734 - 747
• Main Authors: Long, Ze, Dou, Pengcheng, Cai, Weiliang, Mao, Minzhi, Wu, Ren
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 03.02.2023
• Subjects: Animals; Bone Morphogenetic Protein 3; Cell Differentiation - genetics; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Osteogenesis - genetics; Osteoporosis - genetics; Osteoporosis - metabolism; Research Paper; BMP3; osteogenesis; miR-181a-5p; MC3T3-E1; senile osteoporosis
• DOI: 10.18632/aging.204505
• ISSN: 1945-4589

High-throughput microRNA (miRNA) sequencing of osteoporosis was analyzed from the Gene Expression Omnibus (GEO) database to investigate specific microRNAs that control osteogenesis. MiR-181a-5p was differentially expressed among healthy subjects and those with osteoporosis. Inhibitors and mimics were transfected into cells to modulate miR-181a-5p levels to examine the role in MC3T3-E1 functions. Alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining were used for morphological detection, and proteins of ALP and Runt-related transcription factor 2 (RUNX2), as osteogenesis markers, were detected. During the osteogenic differentiation of MC3T3-E1, the transcription level of miR-181a-5p was significantly increased. The inhibition of miR-181a-5p suppressed MC3T3-E1 osteogenic differentiation, whereas its overexpression functioned oppositely. Consistently, the miR-181a-5p antagomir aggravated osteoporosis in old mice. Additionally, we predicted potential target genes via TargetScan and miRDB and identified bone morphogenetic protein 3 (BMP3) as the target gene. Moreover, the reduced expression of miR-181a-5p was validated in our hospitalized osteoporotic patients. These findings have substantial implications for the strategies targeting miR-181a-5p to prevent osteoporosis and potential related fractures.