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

AbstractAs 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.