Cheng Lin1, Wenjun Zhong1, Wei Yan1, Jinsong Yang1, Weiwei Zheng2, Qin Wu3. 1. Department of Orthopedics, Clinic Medical College of Anhui Medical University, the First People's Hospital of Chuzhou City, Chuzhou, Anhui, China. 2. Department of Orthopedics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China. 3. Department of Ultrasound, the Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Abstract
BACKGROUND: Osteoporosis is a disease characterized by bone loss, imbalance of bone metabolism and destruction of trabecular microarchitecture. Circular RNAs (circRNAs) have been revealed as important biological regulators in human diseases. The expression characteristics and mechanism of circRNAs in osteoporosis are unclear. METHODS: The binding sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were predicted using circAtlas (http://circatlas.biols.ac.cn) and miRDB (http://mirdb.org). Target sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were confirmed by a dual luciferase assay. The relationship between miR-516b-5p and AKAP2 was determined by a quantitative reverse transcriptase-polymerase chain reaction. Alizarin red S staining and alkaline phosphatase staining were used to observe the level of osteogenic differentiation after transfection. RESULTS: The first six circRNAs captured from the 30 circRNAs with highest expression in the bone marrow were examined in a mouse model of osteoporosis and the expression of circ-SLC8A1 was found to be significantly reduced in osteoporosis. Circ-SLC8A1 negatively regulated the expression of miR-516b-5p. Overexpression of circ-SLC8A1 blocked the inhibition of AKAP2 by miR-516b-5p. CONCLUSIONS: Circ-SLC8A1 blocks the inhibitory effect of miR-516b-5p on the downstream target gene AKAP2 and promotes osteoporosis. The findings of the present might help to provide a new strategy for the treatment of osteoporosis.
BACKGROUND:Osteoporosis is a disease characterized by bone loss, imbalance of bone metabolism and destruction of trabecular microarchitecture. Circular RNAs (circRNAs) have been revealed as important biological regulators in human diseases. The expression characteristics and mechanism of circRNAs in osteoporosis are unclear. METHODS: The binding sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were predicted using circAtlas (http://circatlas.biols.ac.cn) and miRDB (http://mirdb.org). Target sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were confirmed by a dual luciferase assay. The relationship between miR-516b-5p and AKAP2 was determined by a quantitative reverse transcriptase-polymerase chain reaction. Alizarin red S staining and alkaline phosphatase staining were used to observe the level of osteogenic differentiation after transfection. RESULTS: The first six circRNAs captured from the 30 circRNAs with highest expression in the bone marrow were examined in a mouse model of osteoporosis and the expression of circ-SLC8A1 was found to be significantly reduced in osteoporosis. Circ-SLC8A1 negatively regulated the expression of miR-516b-5p. Overexpression of circ-SLC8A1 blocked the inhibition of AKAP2 by miR-516b-5p. CONCLUSIONS: Circ-SLC8A1 blocks the inhibitory effect of miR-516b-5p on the downstream target gene AKAP2 and promotes osteoporosis. The findings of the present might help to provide a new strategy for the treatment of osteoporosis.