Phosphate ‘sensing’ by human bone

Aim: Osteocytes and osteoblasts produce the humoral factor, FGF23, which maintains serum levels of phosphate and 1, 25 dihydroxy vitamin D within the physiological range. This implies the ability to sense the levels of phosphate in blood and interstitial fluid, however there is no phosphate sensing...

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Main Authors:	Ito, Nobuaki, Kogawa, Masakagi, Wijenayaka, Asiri, Welldon, Katie J, Khalid, Kamarul Ariffin, Ormsby, Renee T, Atkins, Gerald J, Findlay, David M
Format:	Article
Language:	English English
Published:	Springer 2011
Subjects:	QH301 Biology QH426 Genetics R Medicine (General)
Online Access:	http://irep.iium.edu.my/65044/ http://irep.iium.edu.my/65044/ http://irep.iium.edu.my/65044/ http://irep.iium.edu.my/65044/20/65044-abstract.PDF http://irep.iium.edu.my/65044/21/65044%20Phosphate%20%E2%80%98sensing%E2%80%99%20in%20human%20bone-poster.pdf

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spelling	iium-650442018-09-13T03:03:16Z http://irep.iium.edu.my/65044/ Phosphate ‘sensing’ by human bone Ito, Nobuaki Kogawa, Masakagi Wijenayaka, Asiri Welldon, Katie J Khalid, Kamarul Ariffin Ormsby, Renee T Atkins, Gerald J Findlay, David M QH301 Biology QH426 Genetics R Medicine (General) Aim: Osteocytes and osteoblasts produce the humoral factor, FGF23, which maintains serum levels of phosphate and 1, 25 dihydroxy vitamin D within the physiological range. This implies the ability to sense the levels of phosphate in blood and interstitial fluid, however there is no phosphate sensing mechanism has been identified in humans. In this study we investigated the ability of bone tissue to sense phosphate. Methods: We obtained human trabecular bone samples from patients undergoing total hip replacement. Samples were incubated with different concentrations of phosphate with or without dihydroxy vitamin D in the media (phosphate: 1.0mM to 10mM, 1, 25 dihydroxy vitamin D: 0 or 10nM). After 24 to 72 hours, RNA was extracted for measurement by qPCR of mRNA corresponding to phosphate homeostasis or bone formation related genes, such as FGF23, PHEX, DMP1, GALNT3 and SOST. Results: Gene expression in human bone samples was differentially regulated by phosphate in a time and dose dependent. The clearest effects were seen after 72 h treatment and the co-presence of 1, 25 dihydroxy vitamin D (10nM) increased the responses of FGF23, PHEX, DMP1 and SOST mRNA levels to phosphate. After 72 hours treatment with phosphate at 2.5 or 5.0mM, expression of each of FGF23, PHEX, DMP1 and SOST mRNA was increased. GALNT3 was up-regulated by phosphate at 24 hour. Conclusions: These results showed the possibility that extracellular phosphate can be sensed by cells in the bone and that a high phosphate level can stimulate the production of FGF23 or perhaps prevent the cleavage of FGF23 via up-regulation of GALNT3. High levels of 1, 25 dihydroxy vitamin D enhanced these responses. The results also suggested that high phosphate may prevent bone formation by increasing sclerostin expression. Springer 2011-09 Article PeerReviewed application/pdf en http://irep.iium.edu.my/65044/20/65044-abstract.PDF application/pdf en http://irep.iium.edu.my/65044/21/65044%20Phosphate%20%E2%80%98sensing%E2%80%99%20in%20human%20bone-poster.pdf Ito, Nobuaki and Kogawa, Masakagi and Wijenayaka, Asiri and Welldon, Katie J and Khalid, Kamarul Ariffin and Ormsby, Renee T and Atkins, Gerald J and Findlay, David M (2011) Phosphate ‘sensing’ by human bone. Osteoporosis International With other metabolic bone diseases, 22 (Supplement 4). S585-S585. ISSN 0937-941X E-ISSN 1433-2965 https://link.springer.com/article/10.1007/s00198-011-1717-8 10.1007/s00198-011-1717-8
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	QH301 Biology QH426 Genetics R Medicine (General)
spellingShingle	QH301 Biology QH426 Genetics R Medicine (General) Ito, Nobuaki Kogawa, Masakagi Wijenayaka, Asiri Welldon, Katie J Khalid, Kamarul Ariffin Ormsby, Renee T Atkins, Gerald J Findlay, David M Phosphate ‘sensing’ by human bone
description	Aim: Osteocytes and osteoblasts produce the humoral factor, FGF23, which maintains serum levels of phosphate and 1, 25 dihydroxy vitamin D within the physiological range. This implies the ability to sense the levels of phosphate in blood and interstitial fluid, however there is no phosphate sensing mechanism has been identified in humans. In this study we investigated the ability of bone tissue to sense phosphate. Methods: We obtained human trabecular bone samples from patients undergoing total hip replacement. Samples were incubated with different concentrations of phosphate with or without dihydroxy vitamin D in the media (phosphate: 1.0mM to 10mM, 1, 25 dihydroxy vitamin D: 0 or 10nM). After 24 to 72 hours, RNA was extracted for measurement by qPCR of mRNA corresponding to phosphate homeostasis or bone formation related genes, such as FGF23, PHEX, DMP1, GALNT3 and SOST. Results: Gene expression in human bone samples was differentially regulated by phosphate in a time and dose dependent. The clearest effects were seen after 72 h treatment and the co-presence of 1, 25 dihydroxy vitamin D (10nM) increased the responses of FGF23, PHEX, DMP1 and SOST mRNA levels to phosphate. After 72 hours treatment with phosphate at 2.5 or 5.0mM, expression of each of FGF23, PHEX, DMP1 and SOST mRNA was increased. GALNT3 was up-regulated by phosphate at 24 hour. Conclusions: These results showed the possibility that extracellular phosphate can be sensed by cells in the bone and that a high phosphate level can stimulate the production of FGF23 or perhaps prevent the cleavage of FGF23 via up-regulation of GALNT3. High levels of 1, 25 dihydroxy vitamin D enhanced these responses. The results also suggested that high phosphate may prevent bone formation by increasing sclerostin expression.
format	Article
author	Ito, Nobuaki Kogawa, Masakagi Wijenayaka, Asiri Welldon, Katie J Khalid, Kamarul Ariffin Ormsby, Renee T Atkins, Gerald J Findlay, David M
author_facet	Ito, Nobuaki Kogawa, Masakagi Wijenayaka, Asiri Welldon, Katie J Khalid, Kamarul Ariffin Ormsby, Renee T Atkins, Gerald J Findlay, David M
author_sort	Ito, Nobuaki
title	Phosphate ‘sensing’ by human bone
title_short	Phosphate ‘sensing’ by human bone
title_full	Phosphate ‘sensing’ by human bone
title_fullStr	Phosphate ‘sensing’ by human bone
title_full_unstemmed	Phosphate ‘sensing’ by human bone
title_sort	phosphate ‘sensing’ by human bone
publisher	Springer
publishDate	2011
url	http://irep.iium.edu.my/65044/ http://irep.iium.edu.my/65044/ http://irep.iium.edu.my/65044/ http://irep.iium.edu.my/65044/20/65044-abstract.PDF http://irep.iium.edu.my/65044/21/65044%20Phosphate%20%E2%80%98sensing%E2%80%99%20in%20human%20bone-poster.pdf
first_indexed	2023-09-18T21:32:17Z
last_indexed	2023-09-18T21:32:17Z
_version_	1777412590988689408

Phosphate ‘sensing’ by human bone

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