MicroRNA expression profiling in an ovariectomized rat model of postmenopausal osteoporosis before and after estrogen treatment

Am J Transl Res. 2020 Aug 15;12(8):4251-4263. eCollection 2020.

Abstract

Postmenopausal osteoporosis (PMOP) is a common disease that seriously threatens human health. Estrogen deficiency plays an essential role in the pathogenesis of PMOP. MicroRNAs (miRNAs) are involved in the development and progression of PMOP. Therefore, identification of miRNAs in PMOP due to estrogen deficiency may contribute to earlier diagnosis and better treatment of this disease. The rat model of PMOP was established by ovariectomy. After one month of treatment, the knee joints were evaluated by microcomputed tomography and histological analysis. The plasma estrogen levels were quantified by enzyme-linked immunosorbent assays (ELISAs). MiRNA levels were analyzed by high-throughput sequencing and validated using quantitative real-time PCR (qRT-PCR). Two months after ovariectomy, osteoporosis occurred in the subchondral bone of the rats in the PMOP group, while fewer symptoms of osteoporosis occurred in the subchondral bone of the rats with estrogen replacement therapy. Cartilage degeneration was detected in the PMOP group. MiR-29a-3p, miR-93-5p, and miR-486 expression decreased in the PMOP group compared to the control group. After estrogen treatment for one month, the plasma levels of miR-29a-3p, miR-93-5p, and miR-486 recovered to the normal levels. Estrogen eliminated the expression changes in miR-29a-3p, miR-93-5p, and miR-486. The identification of these differentially expressed miRNAs will help elucidate the crucial role of miRNAs in the pathogenesis of PMOP. Our data could lead to the potential utilization of miRNAs in the diagnosis of PMOP and provide a possible therapeutic target for treatment of this disease.

Keywords: Postmenopause; estrogens; microRNAs; osteoporosis; rats.