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

Zachary C. Ryan, Theodore A. Craig, Meghan Elizabeth McGee Lawrence, Jennifer J. Westendorf, Rajiv Kumar

Research output: Contribution to journalReview article

7 Citations (Scopus)

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)2D) 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)2D. 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'.

Original languageEnglish (US)
Pages (from-to)225-231
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume148
DOIs
StatePublished - Jan 1 2015

Fingerprint

Metabolites
Parathyroid Hormone
Vitamin D
Bone
Calcium
Bone and Bones
Phosphorus
Osteoblasts
Knockout Mice
Genes
Osteocytes
Physiologic Calcification
Catenins
Gene Knockout Techniques
Endocrine System
Physiology
Osteoclasts
Epoprostenol
Minerals
fibroblast growth factor 23

Keywords

  • 1,25(OH)D
  • Cyp27b1
  • FGF-23
  • PTH
  • Sclerostin
  • Urinary calcium

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

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. / Ryan, Zachary C.; Craig, Theodore A.; McGee Lawrence, Meghan Elizabeth; Westendorf, Jennifer J.; Kumar, Rajiv.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 148, 01.01.2015, p. 225-231.

Research output: Contribution to journalReview article

@article{1d77e945a90c4344974583feacfa7d74,
title = "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",
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)2D) 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)2D. 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'.",
keywords = "1,25(OH)D, Cyp27b1, FGF-23, PTH, Sclerostin, Urinary calcium",
author = "Ryan, {Zachary C.} and Craig, {Theodore A.} and {McGee Lawrence}, {Meghan Elizabeth} and Westendorf, {Jennifer J.} and Rajiv Kumar",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.jsbmb.2014.11.021",
language = "English (US)",
volume = "148",
pages = "225--231",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - 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

AU - Ryan, Zachary C.

AU - Craig, Theodore A.

AU - McGee Lawrence, Meghan Elizabeth

AU - Westendorf, Jennifer J.

AU - Kumar, Rajiv

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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)2D) 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)2D. 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'.

AB - 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)2D) 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)2D. 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'.

KW - 1,25(OH)D

KW - Cyp27b1

KW - FGF-23

KW - PTH

KW - Sclerostin

KW - Urinary calcium

UR - http://www.scopus.com/inward/record.url?scp=84989788916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989788916&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2014.11.021

DO - 10.1016/j.jsbmb.2014.11.021

M3 - Review article

C2 - 25446885

AN - SCOPUS:84989788916

VL - 148

SP - 225

EP - 231

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

ER -