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The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures

Houston, D A; Myers, K; MacRae, V E; Staines, K A; Farquharson, C


D A Houston

K Myers

V E MacRae

K A Staines

C Farquharson


Sustained exposure to high levels of parathyroid hormone (PTH), as observed in hyperparathyroidism, are catabolic to bone. The increase in the RANKL/OPG ratio in response to continuous PTH, resulting in increased osteoclastogenesis is well established. However, the effects of prolonged PTH exposure on key regulators of skeletal mineralisation has yet to be investigated. This study sought to examine the temporal expression of PHOSPHO1, TNAP and nSMase2 in mineralising osteoblast-like cell cultures and to investigate the effects of continuous PTH exposure on the expression of these genes in vitro. PHOSPHO1, nSMase2 and TNAP expression in cultured MC3T3-C14 cells significantly increased from day 0 to day 10. PTH induced a rapid downregulation of Phospho1 and Smpd3 gene expression in MC3T3-C14 cells and cultured hemi-calvariae. Alpl was differentially regulated by PTH, displaying upregulation in cultured MC3T3-C14 cells and downregulation in hemi-calvariae. The effects of PTH on Phospho1 expression were mimicked with the cAMP agonist forskolin, and blocked by the PKA inhibitor PKI (5-24), highlighting a role for the cAMP/PKA pathway in this regulation. The potent down-regulation of Phospho1 and Smpd3 in osteoblasts in response to continuous PTH may provide a novel explanation for the catabolic effects on the skeleton of such an exposure. Furthermore, our findings support the hypothesis that PHOSPHO1, nSMase2 and TNAP function cooperatively in the initiation of skeletal mineralisation.


Houston, D. A., Myers, K., MacRae, V. E., Staines, K. A., & Farquharson, C. (2016). The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures. Calcified Tissue International, 99(5), 510-524.

Journal Article Type Article
Acceptance Date Jul 12, 2016
Online Publication Date Jul 21, 2016
Publication Date 2016-11
Deposit Date Jan 13, 2017
Publicly Available Date Jan 27, 2017
Journal Calcified Tissue International
Print ISSN 0171-967X
Electronic ISSN 1432-0827
Publisher BMC
Peer Reviewed Peer Reviewed
Volume 99
Issue 5
Pages 510-524
Keywords Endocrinology, Diabetes and Metabolism; Endocrinology; Orthopedics and Sports Medicine
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© The Author(s) 2016
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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