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Association of FGF23 to bone mineral density is dependent on total body fat mass
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
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(English)Manuscript (Other academic)
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-97059OAI: oai:DiVA.org:uu-97059DiVA: diva2:171841
Available from: 2008-04-18 Created: 2008-04-18 Last updated: 2014-11-06
In thesis
1. FGF23 - a possible Phosphatonin
Open this publication in new window or tab >>FGF23 - a possible Phosphatonin
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Human physiology is dependent on an accurate phosphate (Pi) homeostasis. Defective Pi regulation causes hyper- or hypophosphatemia, which are associated with ectopic calcification or impaired bone mineralization, and a shortened life span. Current endocrine models of Pi homeostasis are incomplete. However, studies of acquired and hereditary disorders of Pi homeostasis have revealed new potential Pi regulating hormones, Phosphatonin(s). One of these is fibroblast growth factor-23 (FGF23). FGF23 is produced in bone and is secreted into the circulation. Mutations in FGF23 causes disturbed Pi regulation, without the appropriate counter-regulatory actions of parathyroid hormone or vitamin D. By the generation of FGF23 transgenic mice, which display phenotypic similarities to patients with hypophosphatemic disorders, we show that FGF23 exerts endocrine actions in the kidney and causes osteomalacia. Renal FGF23 actions severely decrease Pi reabsorption and expression of Klotho, a suggested age suppressor gene, known to be crucial in FGF23 receptor binding and activation. In bone, our transgenic model displays impaired osteoclast polarization, which should be detrimental to osteoclastic bone resorption in osteomalacia. However, in our model osteoclasts efficiently participate in bone matrix degradation. Furthermore, we investigated a large population-based cohort in order to elucidate the role of FGF23 in normal physiology. Importantly, we were able to demonstrate an association of FGF23 to parathyroid hormone, renal function and bone mineral density and we found a correlation of FGF23 to weight and body fat mass. The studies on which this thesis is based, demonstrate that FGF23 has phosphatonin-like properties and that the skeleton functions as an endocrine organ. In addition, the results indicate that FGF23 has a role in bone mineral and lipid metabolism, and that FGF23 is a possible diagnostic marker and therapeutic target for the future.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 333
Keyword
Surgery, Fibroblast growth factor 23, FGF23, FGF-23, Phosphate homeostasis, Vitamin D, Klotho, Parathyroid hormone, PTH, Kirurgi
Identifiers
urn:nbn:se:uu:diva-8649 (URN)978-91-554-7165-1 (ISBN)
Public defence
2008-05-09, Rosénsalen, Akademiska Sjukhuset (Barnsjukhuset), Ingång 95/96, Uppsala, 09:15
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Available from: 2008-04-18 Created: 2008-04-18 Last updated: 2013-12-05Bibliographically approved

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Marsell, RichardJonsson, Kenneth B

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