ArticleArthritis research & therapy2012
The effects of oxygen tension and antiaging factor Klotho on Wnt signaling in nucleus pulposus cells.
Article in Arthritis research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Blood and lymphatic vascular remodeling in intervertebral disc degeneration.Frontiers in immunology · 2026Review
- Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation.Theranostics · 2024Article
- Article
- Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications.Frontiers in molecular biosciences · 2023Review
- Lumbar spine abnormalities in patients with obstructive sleep apnoea.Scientific reports · 2021Article
- Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration.International journal of molecular medicine · 2021Article
- Antiaging Factor Klotho Retards the Progress of Intervertebral Disc Degeneration through the Toll-Like Receptor 4-NF-International journal of cell biology · 2020Article
- αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight.Cellular and molecular life sciences : CMLS · 2019Review
- Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation.Oncotarget · 2017Review
- Molecular basis of Klotho: from gene to function in aging.Endocrine reviews · 2015Review
- The aging mouse partially models the aging human spine: lumbar and coccygeal disc height, composition, mechanical properties, and Wnt signaling in young and old mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Article
- Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klotho.Journal of perinatal medicine · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe goals of this study were to examine the oxemic regulation of Wnt signaling to explore whether Wnt signaling accelerates the age-related degeneration of nucleus pulposus cells, and if so, to define the mechanism underlying this effect. We investigated the expression of Klotho, a newly identified antiaging gene, and whether its regulation is attributable to the suppression of Wnt signaling.
methodsRat nucleus pulposus cells were cultured under normoxic (21% O2) or hypoxic (2% O2) conditions, and the expression and promoter activity of Wnt signaling and Klotho were evaluated. The effect of Klotho protein was examined with transfection experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, senescence-associated β-galactosidase staining, and cell-cycle analysis. To determine the methylation status of the Klotho promoter region, bisulfite genomic sequencing analysis was performed. Its relation with the activation of Wnt signaling was assessed. We also examined whether the expression of Klotho could block the effects of pathological Wnt expression in nucleus pulposus cells.
resultsNucleus pulposus cells exhibited increased β-catenin mRNA and protein under the hypoxic condition. Klotho protein was expressed in vivo, and protein and messenger RNA expression decreased under the hypoxic condition. Klotho treatment decreased cell proliferation and induced the quiescence of nucleus pulposus cells. In addition, Klotho treatment inhibited expression of β-catenin gene and protein compared with untreated control cells.
conclusionsThese data indicate that Wnt signaling and Klotho form a negative-feedback loop in nucleus pulposus cells. These results suggest that the expression of Klotho is regulated by the balance between upregulation and downregulation of Wnt signaling.
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