ArticleJCI insight2019
Vitamin D-regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Sclerostin in Vascular Calcification: Hypoxia-Driven Regulation and Therapeutic Modulation by Natural Products.Current atherosclerosis reports · 2026Review
- The Bone-Vascular Axis: A Key Player in Chronic Kidney Disease Associated Vascular Calcification.Kidney diseases (Basel, Switzerland) · 2024Review
- The Relationship between Sclerostin and Kidney Transplantation Mineral Bone Disorders: A Molecule of Controversies.Calcified tissue international · 2024Review
- Vascular, valvular and kidney calcification manifested in mouse models of adenine-induced chronic kidney disease.Renal failure · 2023Article
- Impaired 1,25-dihydroxyvitamin D3 action underlies enthesopathy development in the Hyp mouse model of X-linked hypophosphatemia.JCI insight · 2023Article
- Wnt/β-catenin pathway inhibitors, bone metabolism and vascular health in kidney transplant patients.Journal of nephrology · 2023Observational
- Updates in the chronic kidney disease-mineral bone disorder show the role of osteocytic proteins, a potential mechanism of the bone-Vascular paradox, a therapeutic target, and a biomarker.Frontiers in physiology · 2023Review
- Novel insights into osteocyte and inter-organ/tissue crosstalk.Frontiers in endocrinology · 2023Review
- Article
- Uremic mouse model to study vascular calcification and "inflamm-aging".Journal of molecular medicine (Berlin, Germany) · 2022Article
- Vascular Calcification: New Insights Into BMP Type I Receptor A.Frontiers in pharmacology · 2022Review
- Do Interactions of Vitamin DCurrent osteoporosis reports · 2021Review
- Inflammation: a putative link between phosphate metabolism and cardiovascular disease.Clinical science (London, England : 1979) · 2021Review
- Article
- The relationship between sclerostin and carotid artery atherosclerosis in patients with stage 3-5 chronic kidney disease.International urology and nephrology · 2020Article
- The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification.International journal of molecular sciences · 2020Review
- Associations of Serum Dickkopf-1 and Sclerostin With Cardiovascular Events: Results From the Prospective Bruneck Study.Journal of the American Heart Association · 2020Observational
- Pathophysiological and Genetic Aspects of Vascular Calcification.Cardiology research and practice · 2020Review
- Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3.Cell death & disease · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We induced chronic kidney disease (CKD) with adenine in WT mice, mice with osteocyte-specific deletion of Cyp27b1, encoding the 25-hydroxyvitamin D 1(OH)ase [Oct-1(OH)ase-/-], and mice with global deletion of Cyp27b1 [global-1α(OH)ase-/-]; we then compared extraskeletal calcification. After adenine treatment, mice displayed increased blood urea nitrogen, decreased serum 1,25(OH)2D, and severe hyperparathyroidism. Skeletal expression of Cyp27b1 and of sclerostin and serum sclerostin all increased in WT mice but not in Oct-1α(OH)ase-/- mice or global-1α(OH)ase-/- mice. In contrast, skeletal expression of BMP2 and serum BMP2 rose in the Oct-1α(OH)ase-/- mice and in the global-1α(OH)ase-/- mice. Extraskeletal calcification occurred in muscle and blood vessels of mice with CKD and was highest in Oct-1α(OH)ase-/-mice. In vitro, recombinant sclerostin (100 ng/mL) significantly suppressed BMP2-induced osteoblastic transdifferentiation of vascular smooth muscle A7r5 cells and diminished BMP2-induced mineralization. Our study provides evidence that local osteocytic production of 1,25(OH)2D stimulates sclerostin and inhibits BMP2 production in murine CKD, thus mitigating osteoblastic transdifferentiation and mineralization of soft tissues. Increased osteocytic 1,25(OH)2D production, triggered by renal malfunction, may represent a "primary defensive response" to protect the organism from ectopic calcification by increasing sclerostin and suppressing BMP2 production.
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