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7-Ketocholesterol-Induced Micro-RNA-107-5p Increases Number and Activity of Osteoclasts by Targeting MKP1
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 7; Pages: 3697
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- Osteoclasts (OCs), which are responsible for bone resorption, play a critical role in cholesterol-induced bone loss and recent studies have suggested that various micro-RNAs (miRs) contribute to modulating OCs. We hypothesized that 7-ketocholesterol (7-KC), a metabolite responsible for cholesterol-induced bone loss, induces miR-107-5p, which affects OCs. Overexpression and knock-down of miR-107-5p were performed using miR-107-5p mimic and anti-miR-107-5p, respectively. The effects of miR-107-5p on OCs were analyzed by tartrate-resistant alkaline phosphatase staining, qPCR, and Western blot. MiR-107-5p was upregulated after 7-KC exposure in receptor activator of nuclear factor kappa-Β ligand-stimulated OCs. Furthermore, miR-107-5p upregulation was also observed in tibiae from an atherogenic diet-fed mice compared with mice fed with a normal diet. MiR-107-5p overexpression enhanced the area and number of OCs, whereas inhibiting the endogenous expression of miR-107-5p generated by 7-KC had the opposite effect. Among the possible candidates, mitogen-activated protein kinase phosphatase-1, a stress-responsive dual-specificity phosphatase that inactivates mitogen-activated protein kinase (MKP1), has been proven to be a target gene of miR-107-5p, as demonstrated by the direct interaction between miR-107-5p and the 3′-untranslated region of MKP1. Collectively, our findings demonstrate that 7-KC-induced miR-107-5p promotes differentiation and function of OCs by downregulating MKP1.
- Subjects :
- Organic Chemistry
Osteoclasts
Cell Differentiation
General Medicine
Catalysis
Computer Science Applications
Inorganic Chemistry
Mice
MicroRNAs
Animals
Physical and Theoretical Chemistry
Bone Resorption
7-ketocholesterol
micro-RNA-107-5p
osteoclast
mitogen-activated protein kinase phosphatase 1
Molecular Biology
3' Untranslated Regions
Ketocholesterols
Spectroscopy
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 23; Issue 7; Pages: 3697
- Accession number :
- edsair.doi.dedup.....5c09da16a1d9f26e879c17da6531bd57
- Full Text :
- https://doi.org/10.3390/ijms23073697