Hsa_circ_0002060 Knockdown Ameliorates Osteoporosis by Targeting MiR-198-5p

Abstract

Osteoporosis (OP) is increasingly becoming one of a major health concerns all over the world. However, the limitations of current therapeutic drugs for OP are including considerable side effects and low efficacy. Therefore, it is required to develop new therapeutic drugs for OP. This study aimed to investigate the role of hsa_circ_0002060 in the regulation of osteoporosis. Osteoblast cells (hFOB 1.19) were transfected with hsa_circ_0002060 small interfering RNA (siRNA), following by stimulated with dexamethasone (DEX) to mimic OP in vitro. Cell counting kit-8, apoptosis, and JC-1 mitochondrial membrane potential assays were used to evaluate the cell viability, apoptosis, and mitochondrial membrane potential, respectively. Western blot was conducted to detect the expression of proteins. In addition, the levels of reactive oxygen species, superoxide dismutase, glutathione and malondialdehyde were measured with enzyme-linked immunosorbent assay (ELISA). The putative target of hsa_circ_0002060 was verified by dual luciferase reporter assay and RNA pull down. At last, the role of hsa_circ_0002060 in the progression of OP was investigated with an ovariectomy (OVX)-induced OP mouse model. The results indicated DEX could induce cell viability decline in hFOB 1.19 cells, which was ameliorated by hsa_circ_0002060 knockdown. Consistently, DEX-induced cell apoptosis of hFOB 1.19 was ameliorated by hsa_circ_0002060 knockdown as well. As for the underlying mechanisms study, hsa_circ_0002060 was proved to regulate the viability of hFOB 1.19 cells through targeting miR-198-5p/Bax axis. Additionally, hsa_circ_0002060 knockdown alleviated ovariectomy-induced OP in a mouse model. Taken together, hsa_circ_0002060 knockdown alleviated the progression of OP by targeting miR-198-5p. Hsa_circ_0002060 might possibly be served as a therapeutic target for treating OP.

Graphical Abstract