Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3

Asiri R. Wijenayaka, Matthew Prideaux, Dongqing Yang, Howard A. Morris, David M. Findlay, Paul H. Anderson, Gerald J. Atkins

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The osteocyte expressed gene SOST encodes sclerostin, a potent negative regulator of bone formation and inducer of bone resorption. We have recently demonstrated that the human SOST gene is positively regulated in response to 1α,25-dihydroxyvitamin D3 (1,25D). Responsiveness may be mediated at least in part by a single classical DR3-type vitamin D response element (VDRE). In this study we examined the early responsiveness of the SOST gene to both 1,25D and to parathyroid hormone (PTH), a known repressor of SOST expression, in SaOS2 cells differentiated to an osteocyte-like stage of cell maturation. Both SOST mRNA levels and sclerostin protein levels increased in these cultures as early as 3 h post-treatment with 1,25D and declined in response to PTH in the same timeframe. For 1,25D, the level of induced SOST appeared dependent on the extent, to which the degradative enzyme 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) was induced. Together with the observed rapid decrease in SOST/sclerostin levels in response to PTH, endocrine regulation of sclerostin production appears to be an important determinant of sclerostin levels. These findings confirm that the human SOST gene and sclerostin expression can be considered to be directly 1,25D-responsive in osteocytes.

Original languageEnglish (US)
Pages (from-to)369-373
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume164
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Fingerprint

Calcitriol
Osteocytes
Genes
Parathyroid Hormone
Bone
Vitamin D Response Element
Bone Resorption
Mixed Function Oxygenases
Osteogenesis
Gene Expression
Messenger RNA
Enzymes
Proteins

Keywords

  • 1,25-Dihydoxyvitamin D
  • Osteocyte
  • Sclerostin

ASJC Scopus subject areas

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

Cite this

Wijenayaka, A. R., Prideaux, M., Yang, D., Morris, H. A., Findlay, D. M., Anderson, P. H., & Atkins, G. J. (2016). Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3 Journal of Steroid Biochemistry and Molecular Biology, 164, 369-373. https://doi.org/10.1016/j.jsbmb.2015.12.006

Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3 . / Wijenayaka, Asiri R.; Prideaux, Matthew; Yang, Dongqing; Morris, Howard A.; Findlay, David M.; Anderson, Paul H.; Atkins, Gerald J.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 164, 01.11.2016, p. 369-373.

Research output: Contribution to journalArticle

Wijenayaka, AR, Prideaux, M, Yang, D, Morris, HA, Findlay, DM, Anderson, PH & Atkins, GJ 2016, 'Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3 ', Journal of Steroid Biochemistry and Molecular Biology, vol. 164, pp. 369-373. https://doi.org/10.1016/j.jsbmb.2015.12.006
Wijenayaka, Asiri R. ; Prideaux, Matthew ; Yang, Dongqing ; Morris, Howard A. ; Findlay, David M. ; Anderson, Paul H. ; Atkins, Gerald J. / Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3 In: Journal of Steroid Biochemistry and Molecular Biology. 2016 ; Vol. 164. pp. 369-373.
@article{834c3505c8b14b4b9190b03c331996a1,
title = "Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3",
abstract = "The osteocyte expressed gene SOST encodes sclerostin, a potent negative regulator of bone formation and inducer of bone resorption. We have recently demonstrated that the human SOST gene is positively regulated in response to 1α,25-dihydroxyvitamin D3 (1,25D). Responsiveness may be mediated at least in part by a single classical DR3-type vitamin D response element (VDRE). In this study we examined the early responsiveness of the SOST gene to both 1,25D and to parathyroid hormone (PTH), a known repressor of SOST expression, in SaOS2 cells differentiated to an osteocyte-like stage of cell maturation. Both SOST mRNA levels and sclerostin protein levels increased in these cultures as early as 3 h post-treatment with 1,25D and declined in response to PTH in the same timeframe. For 1,25D, the level of induced SOST appeared dependent on the extent, to which the degradative enzyme 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) was induced. Together with the observed rapid decrease in SOST/sclerostin levels in response to PTH, endocrine regulation of sclerostin production appears to be an important determinant of sclerostin levels. These findings confirm that the human SOST gene and sclerostin expression can be considered to be directly 1,25D-responsive in osteocytes.",
keywords = "1,25-Dihydoxyvitamin D, Osteocyte, Sclerostin",
author = "Wijenayaka, {Asiri R.} and Matthew Prideaux and Dongqing Yang and Morris, {Howard A.} and Findlay, {David M.} and Anderson, {Paul H.} and Atkins, {Gerald J.}",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.jsbmb.2015.12.006",
language = "English (US)",
volume = "164",
pages = "369--373",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Early response of the human SOST gene to stimulation by 1α,25-dihydroxyvitamin D3

AU - Wijenayaka, Asiri R.

AU - Prideaux, Matthew

AU - Yang, Dongqing

AU - Morris, Howard A.

AU - Findlay, David M.

AU - Anderson, Paul H.

AU - Atkins, Gerald J.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - The osteocyte expressed gene SOST encodes sclerostin, a potent negative regulator of bone formation and inducer of bone resorption. We have recently demonstrated that the human SOST gene is positively regulated in response to 1α,25-dihydroxyvitamin D3 (1,25D). Responsiveness may be mediated at least in part by a single classical DR3-type vitamin D response element (VDRE). In this study we examined the early responsiveness of the SOST gene to both 1,25D and to parathyroid hormone (PTH), a known repressor of SOST expression, in SaOS2 cells differentiated to an osteocyte-like stage of cell maturation. Both SOST mRNA levels and sclerostin protein levels increased in these cultures as early as 3 h post-treatment with 1,25D and declined in response to PTH in the same timeframe. For 1,25D, the level of induced SOST appeared dependent on the extent, to which the degradative enzyme 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) was induced. Together with the observed rapid decrease in SOST/sclerostin levels in response to PTH, endocrine regulation of sclerostin production appears to be an important determinant of sclerostin levels. These findings confirm that the human SOST gene and sclerostin expression can be considered to be directly 1,25D-responsive in osteocytes.

AB - The osteocyte expressed gene SOST encodes sclerostin, a potent negative regulator of bone formation and inducer of bone resorption. We have recently demonstrated that the human SOST gene is positively regulated in response to 1α,25-dihydroxyvitamin D3 (1,25D). Responsiveness may be mediated at least in part by a single classical DR3-type vitamin D response element (VDRE). In this study we examined the early responsiveness of the SOST gene to both 1,25D and to parathyroid hormone (PTH), a known repressor of SOST expression, in SaOS2 cells differentiated to an osteocyte-like stage of cell maturation. Both SOST mRNA levels and sclerostin protein levels increased in these cultures as early as 3 h post-treatment with 1,25D and declined in response to PTH in the same timeframe. For 1,25D, the level of induced SOST appeared dependent on the extent, to which the degradative enzyme 1,25-dihydroxyvitamin D 24-hydroxylase (CYP24A1) was induced. Together with the observed rapid decrease in SOST/sclerostin levels in response to PTH, endocrine regulation of sclerostin production appears to be an important determinant of sclerostin levels. These findings confirm that the human SOST gene and sclerostin expression can be considered to be directly 1,25D-responsive in osteocytes.

KW - 1,25-Dihydoxyvitamin D

KW - Osteocyte

KW - Sclerostin

UR - http://www.scopus.com/inward/record.url?scp=84960877429&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960877429&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2015.12.006

DO - 10.1016/j.jsbmb.2015.12.006

M3 - Article

VL - 164

SP - 369

EP - 373

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

ER -