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Circular RNA HIPK3 downregulation mediates hydrogen peroxide-induced cytotoxicity in human osteoblasts
- Source :
- Aging (Albany NY)
- Publication Year :
- 2020
- Publisher :
- Impact Journals, LLC, 2020.
-
Abstract
- Hydrogen peroxide (H2O2) induces oxidative injury to human osteoblasts. The expression and potential function of circular RNA HIPK3 (circHIPK3) in H2O2-treated human osteoblasts were tested. We show that H2O2 significantly downregulated circHIPK3 in OB-6 cells and primary human osteoblasts. Furthermore, circHIPK3 levels were decreased in the necrotic femoral head tissues of dexamethasone-treated patients. In OB-6 osteoblastic cells and primary human osteoblasts, forced overexpression of circHIPK3 by a lentiviral construct alleviated H2O2-induced viability reduction, cell death and apoptosis. Contrarily, circHIPK3 silencing by targeted shRNA potentiated H2O2-induced cytotoxicity in OB-6 cells and primary human osteoblasts. Moreover, circHIPK3 downregulation by H2O2 induced miR-124 accumulation in OB-6 cells and primary human osteoblasts. On the contrary, miR-124 inhibition by transfection of the miR-124 inhibitor protected human osteoblasts from H2O2. Importantly, forced overexpression of miR-124 by transfection of the miR-124 mimic induced significant cytotoxicity in OB-6 cells and primary human osteoblasts. H2O2 downregulated miR-124’s targets, cyclin dependent kinase 6 and Rho-Associated Protein Kinase 1, in human osteoblasts. In conclusion circHIPK3 downregulation mediates H2O2-induced cytotoxicity in human osteoblasts.
- Subjects :
- musculoskeletal diseases
Aging
Programmed cell death
oxidative injury
Cell Survival
hydrogen peroxide
Apoptosis
Protein Serine-Threonine Kinases
Ectopic Gene Expression
Small hairpin RNA
Downregulation and upregulation
Humans
RNA, Small Interfering
Cytotoxicity
Protein kinase A
Cells, Cultured
Osteoblasts
Cell Death
biology
Chemistry
Intracellular Signaling Peptides and Proteins
RNA, Circular
Cell Biology
Transfection
circular RNA HIPK3
Cell biology
Gene Expression Regulation
biology.protein
microRNA-124
RNA Interference
Cyclin-dependent kinase 6
Research Paper
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....431aee8a8a34bceeec16dfed71e90f81