ArticleKidney international2009
Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase.
Article in Kidney international, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 192 citations in OpenAlex.
- Can salivary phosphate levels be an early biomarker to monitor the evolvement of obesity?Contributions to nephrology · 2013Trial
- Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.Cardiovascular toxicology · 2026Review
- Klotho revisited: tubular heterogeneity reshapes mineral metabolism, aging, and CKD.Pflugers Archiv : European journal of physiology · 2026Review
- Klotho in the kidney distal convolution regulates urinary Klotho excretion and kidney calcium reabsorption, but not phosphate homeostasis.Kidney international · 2026Article
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Axonal Energy Crisis and Calcium Phosphate Dysregulation as Pathogenesis of Optic Disc Drusen.Aging and disease · 2024Review
- Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice.International journal of molecular sciences · 2024Article
- Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.International journal of molecular sciences · 2024Review
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Relationship of the bone phenotype of the Klotho mutant mouse model of accelerated aging to changes in skeletal architecture that occur with chronological aging.Frontiers in endocrinology · 2024Article
- New concepts in regulation and function of the FGF23.Clinical and experimental medicine · 2023Review
- Fibroblast Growth Factor 23 and Muscle Wasting: A Metabolic Point of View.Kidney international reports · 2023Review
- Association between anemia and serum Klotho in middle-aged and older adults.BMC nephrology · 2023Article
- Interactions between FGF23 and vitamin D.Endocrine connections · 2022Review
- Salivary phosphate as a biomarker for human diseases.FASEB bioAdvances · 2022Article
- The Role of Alterations in Alpha-Klotho and FGF-23 in Kidney Transplantation and Kidney Donation.Frontiers in medicine · 2022Review
- Extrarenal expression of α-klotho, the kidney related longevity gene, in Heterocephalus glaber, the long living Naked Mole Rat.Scientific reports · 2021Article
- Phosphate as a Pathogen of Arteriosclerosis and Aging.Journal of atherosclerosis and thrombosis · 2021Review
- Parathyroid Hormone 1 Receptor Signaling in Dental Mesenchymal Stem Cells: Basic and Clinical Implications.Frontiers in cell and developmental biology · 2021Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Changes in the expression of klotho, a beta-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure. Klotho knockout mice have increased expression of the sodium/phosphate cotransporter (NaPi2a) and 1alpha-hydroxylase in their kidneys, along with increased serum levels of phosphate and 1,25-dihydroxyvitamin D. These changes are associated with widespread soft-tissue calcifications, generalized tissue atrophy, and a shorter lifespan in the knockout mice. To determine the role of the increased vitamin D activities in klotho knockout animals, we generated klotho and 1alpha-hydroxylase double-knockout mice. These double mutants regained body weight and developed hypophosphatemia with a complete elimination of the soft-tissue and vascular calcifications that were routinely found in klotho knockout mice. The markedly increased serum fibroblast growth factor 23 and the abnormally low serum parathyroid hormone levels, typical of klotho knockout mice, were significantly reversed in the double-knockout animals. These in vivo studies suggest that vitamin D has a pathologic role in regulating abnormal mineral ion metabolism and soft-tissue anomalies of klotho-deficient mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.