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Cell Biol Int. 2016 Mar;40(3):329-40. doi: 10.1002/cbin.10573. Epub 2016 Jan 12.

Expression of osteoclastogenic factor transcripts in osteoblast-like UMR-106 cells after exposure to FGF-23 or FGF-23 combined with parathyroid hormone.

Author information

1
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand.
2
Microarray Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand.
3
Office of Academic Management, Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand.
4
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Abstract

As a bone-derived hormone, fibroblast growth factor-23 (FGF-23) negatively regulates phosphate and calcium metabolism, while retaining growth-promoting action for mesenchymal cell differentiation. Elevated FGF-23 levels, together with hyperparathyroidism, are often observed in chronic kidney disease, which is associated with impaired bone mineralization and enhanced bone resorption. Although overexpression of osteoblast-derived osteoclastogenic cytokines might contribute to this metabolic bone disease, whether FGF-23 alone and FGF-23 plus parathyroid hormone (PTH) directly modulated the expression of osteoblast-derived osteoclastogenic genes remained elusive. Herein, we demonstrated the direct effects of FGF-23 on proliferation and mRNA expression of osteoblast-specific differentiation and osteoclastogenic markers in rat osteoblast-like UMR-106 cells in the presence or absence of PTH. FGF-23 was found to suppress UMR-106 cell proliferation, while increasing FGF-23 expression, the latter of which suggested the presence of positive feedback regulation of FGF-23 expression in osteoblasts. FGF-23 also upregulated the mRNA expression of osteoblast differentiation markers (e.g., Runx2, osterix, AJ18, Dlx5, alkaline phosphatase, and osteopontin), osteoclastogenic factors (e.g., MCSF, MCP-1, IL-6, and TNF-α), and bone resorption regulators (RANKL and osteoprotegerin). However, combined PTH and FGF-23 exposure did not alter the levels of FGF-23-induced transcripts, suggesting that both hormones had no additive effect. In conclusion, FGF-23 directly suppressed osteoblast proliferation, while inducing osteoclastogenic gene expression in UMR-106 cells, and the FGF-23-induced transcripts were not altered by long-standing PTH exposure.

KEYWORDS:

cell differentiation; cell proliferation; fibroblast growth factor-23; gene expression; parathyroid hormone

PMID:
26694880
DOI:
10.1002/cbin.10573
[Indexed for MEDLINE]

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