Alterations in vitamin D metabolite, parathyroid hormone and fibroblast growth factor-23 concentrations in sclerostin-deficient mice permit the maintenance of a high bone mass. Issue 148 (April 2015)

• Record Type: Journal Article
• Authors: Ryan, Zachary C.; Craig, Theodore A.; McGee-Lawrence, Meghan; Westendorf, Jennifer J.; Kumar, Rajiv
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 148(2015)
• Page Start: 225
• Page End: 231
• Publication Date: 2015-04
• Subjects: Sclerostin -- 1, 25(OH)2D -- FGF-23 -- PTH -- Urinary calcium -- Cyp27b1; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.11.021
• Languages: English
• ISSNs: 0960-0760

Abstract

Graphical abstract: Highlights: Sost deficiency is associated with increased bone mass and osteoblast activity. Increased serum 1, 25(OH)2 D enhances Ca and P balance in sclerostin deficiency. Reduced FGF-23 concentrations permit phosphorus retention. Hormonal changes facilitate enhanced mineral retention in sclerostin deficiency. Abstract: Humans with mutations of the sclerostin ( SOST ) gene, and knockout animals in which the Sost gene has been experimentally deleted, exhibit an increase in bone mass. We review the mechanisms by which Sost knockout mice are able to accrete increased amounts of calcium and phosphorus required for the maintenance of a high bone mass. Recently published information from our laboratory, shows that bone mass is increased in Sost -deficient mice through an increase in osteoblast and a decrease in osteoclast activity, which is mediated by activation of β-catenin and an increase in prostacyclin synthesis in osteocytes and osteoblasts. The increases in calcium and phosphorus retention required for enhanced bone mineral accretion are brought about by changes in the vitamin D endocrine system, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23). Thus, in Sost knockout mice, concentrations of serum 1, 25-dihydroxyvitamin D (1, 25(OH)2 D) are increased and concentrations of FGF-23 are decreased thereby allowing a positive calcium and phosphorus balance. Additionally, in the absence of Sost expression, urinary calcium is decreased, either through a direct effect of sclerostin on renal calcium handling, or through its effect on the synthesis of 1, 25(OH)2 D. Adaptations in vitamin D, PTH and FGF-23 physiology occur in the absence of sclerostin expression and mediate increased calcium and phosphorus retention required for the increase in bone mineralization. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.