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Phosphate ‘sensing’ by human bone

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

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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.

Item Type: Article (Meeting Abstract)
Additional Information: 2295/65044
Uncontrolled Keywords: Phosphate, human bone
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Medicine > Department of Department of Orthopaedics, Traumatology & Rehabilitation
Kulliyyah of Medicine
Depositing User: Assoc. Prof. Dr. Kamarul Ariffin Khalid
Date Deposited: 13 Sep 2018 11:03
Last Modified: 13 Sep 2018 11:03
URI: http://irep.iium.edu.my/id/eprint/65044

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