Long Yu1, Yonggang Liu2. 1. Orthopedics Department, The 8th Medical Center of Chinese PLA General Hospital, Beijing, 100853, China. 2. Department of Spine Surgery, Boxing People's Hospital, BinZhou, 256500, Shandong, China. Electronic address: erzhongy6798@163.com.
Abstract
BACKGROUND: Circular RNAs (circRNAs) are emerging as important regulators in human disease. The expression profile and mechanism of circRNAs in postmenopausal osteoporosis remains largely unknown. Bone morphogenetic protein 2 (BMP2) is known to play important role in inducing osteogenic differentiation. MiR-98 was reported to regulate osteogenic differentiation of human bone mesenchymal stromal cells by targeting BMP2. AIM: We aimed to analyze circRNA expression profiles in osteoporosis and explore the molecular mechanism of circRNA_0016624 and interaction between circRNA_0016624, miR-98 and BMP2 during osteogenic differentiation. METHODS: RNA-seq and bioinformatics analysis was performed in postmenopausal osteoporosis patients to screen for differentially expressed circRNAs. MiRanda and TargetScan were used to detect miR-98 binding sites of circRNA_0016624 and the target relationship was confirmed by dual luciferase assay. Expression level of circRNA_0016624, miR-98 and BMP2 were measured by qRT-PCR or Western blot. ARS staining was used to observe the level of osteogenic differentiation after transfection. RESULTS: There were 387 circRNAs were differentially expressed in osteoporosis (|fold change| > 2 and P-value < 0.01). circRNA_0016624 and BMP2 were down-regulated in osteoporosis. CircRNA_0016624 could sponge miR-98 and regulate miR-98 expression. Overexpression of circRNA_0016624 promoted the expression of BMP2 and prevented osteoporosis. CONCLUSION: circRNA_0016624 could sponge miR-98 and enhance BMP2 expression, thus circRNA_0016624 prevents osteoporosis and may provide a novel therapeutic strategy.
BACKGROUND: Circular RNAs (circRNAs) are emerging as important regulators in human disease. The expression profile and mechanism of circRNAs in postmenopausal osteoporosis remains largely unknown. Bone morphogenetic protein 2 (BMP2) is known to play important role in inducing osteogenic differentiation. MiR-98 was reported to regulate osteogenic differentiation of human bone mesenchymal stromal cells by targeting BMP2. AIM: We aimed to analyze circRNA expression profiles in osteoporosis and explore the molecular mechanism of circRNA_0016624 and interaction between circRNA_0016624, miR-98 and BMP2 during osteogenic differentiation. METHODS: RNA-seq and bioinformatics analysis was performed in postmenopausal osteoporosispatients to screen for differentially expressed circRNAs. MiRanda and TargetScan were used to detect miR-98 binding sites of circRNA_0016624 and the target relationship was confirmed by dual luciferase assay. Expression level of circRNA_0016624, miR-98 and BMP2 were measured by qRT-PCR or Western blot. ARS staining was used to observe the level of osteogenic differentiation after transfection. RESULTS: There were 387 circRNAs were differentially expressed in osteoporosis (|fold change| > 2 and P-value < 0.01). circRNA_0016624 and BMP2 were down-regulated in osteoporosis. CircRNA_0016624 could sponge miR-98 and regulate miR-98 expression. Overexpression of circRNA_0016624 promoted the expression of BMP2 and prevented osteoporosis. CONCLUSION: circRNA_0016624 could sponge miR-98 and enhance BMP2 expression, thus circRNA_0016624 prevents osteoporosis and may provide a novel therapeutic strategy.