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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.
Insights
This study reveals that inhibiting hsa_circ_0002060 can alleviate osteoporosis progression. Knocking down this circular RNA protected osteoblast cells and reduced bone loss in a mouse model, suggesting its potential as a therapeutic target for osteoporosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Osteoporosis (OP) is a growing global health concern with limited therapeutic options due to side effects and low efficacy.
- Novel therapeutic targets are crucial for developing effective treatments for OP.
Purpose of the Study:
- To investigate the role of hsa_circ_0002060 in the regulation of osteoporosis.
- To explore hsa_circ_0002060 as a potential therapeutic target for OP.
Main Methods:
- Osteoblast cells (hFOB 1.19) were used to mimic OP in vitro using dexamethasone (DEX) and transfected with hsa_circ_0002060 small interfering RNA (siRNA).
- Assays included cell viability (CCK-8), apoptosis, mitochondrial membrane potential (JC-1), protein expression (Western blot), and oxidative stress markers (ELISA).
- Mechanism was explored via dual luciferase reporter and RNA pull-down assays, and in vivo efficacy was tested in an ovariectomy (OVX)-induced OP mouse model.
Main Results:
- Dexamethasone-induced reduction in cell viability and apoptosis in osteoblasts were ameliorated by hsa_circ_0002060 knockdown.
- hsa_circ_0002060 was found to target miR-198-5p, regulating osteoblast viability via the miR-198-5p/Bax axis.
- Knockdown of hsa_circ_0002060 alleviated ovariectomy-induced osteoporosis in a mouse model.
Conclusions:
- hsa_circ_0002060 knockdown alleviates osteoporosis progression by targeting miR-198-5p.
- hsa_circ_0002060 represents a potential therapeutic target for treating osteoporosis.
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