学術雑誌論文

学術雑誌論文

text

PLoS ONE. 2014, 9(4), p. e93840

Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice

PLOS

英語

text

2014-04-07

https://doi.org/10.1371/journal.pone.0093840

Miyagawa K., Yamazaki M., Kawai M., et al. Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice. PLoS ONE 9(4), e93840 (2014); https://doi.org/10.1371/journal.pone.0093840.

Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C. In Hyp mice, a murine model for X-linked hypophosphatemia (XLH), Phex deficiency results in the overproduction of FGF23 in osteocytes, which leads to hypophosphatemia and impaired vitamin D metabolism. In this study, to further clarify the abnormality in osteocytes of Hyp mice, we obtained detailed gene expression profiles in osteoblasts and osteocytes isolated from the long bones of 20-week-old Hyp mice and wild-type (WT) control mice. The expression of Fgf23, Dmp1, and Fam20c was higher in osteocytic cells than in osteoblastic cells in both genotypes, and was up-regulated in Hyp cells. Interestingly, the upregulation of these genes in Hyp bones began before birth. On the other hand, the expression of Slc20a1 encoding the sodium/phosphate (Na⁺/Pi) co-transporter Pit1 was increased in osteoblasts and osteocytes from adult Hyp mice, but not in Hyp fetal bones. The direct effects of extracellular Pi and 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] on isolated osteoblastic and osteocytic cells were also investigated. Twenty-four-hour treatment with 10⁻⁸ M 1,25(OH)₂D₃ increased the expression of Fgf23 in WT osteoblastic cells but not in osteocytic cells. Dmp1 expression in osteocytic cells was increased due to the 24- hour treatment with 10 mM Pi and was suppressed by 10⁻⁸ M 1,25(OH)₂D₃ in WT osteocytic cells. We also found the upregulation of the genes for FGF1, FGF2, their receptors, and Egr-1 which is a target of FGF signaling, in Hyp osteocytic cells, suggesting the activation of FGF/FGFR signaling. These results implicate the complex gene dysregulation in osteoblasts and osteocytes of Hyp mice, which might contribute to the pathogenesis.

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103653

Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice

PLOS

英語

2014-04-07

PLoS ONE

9

4

e93840

https://doi.org/10.1371/journal.pone.0093840

https://hdl.handle.net/11094/103653