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Abstract: SA-OR100

The Osteocyte Is Not the Only Source of FGF23 in Folic Acid-Induced AKI

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic


  • Christov, Marta, New York Medical College, Valhalla, New York, United States
  • Cheng, Zhiqiang, UCSF, San Francisco, California, United States
  • Rabadi, Seham M., New York Medical College, Valhalla, New York, United States
  • Hwong, Jenna, SFVAMC, San Francisco, California, United States
  • Ho, Hanson, Adaptive Biotechnology, South San francisco, California, United States
  • Herberger, Amanda L., University of California, San Francisco/ San Francisco Veterans Affairs Medical Center, San Francsicso, California, United States
  • Jüppner, Harald, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Chang, Wenhan, Endocrine Unit, SF-VAMC, University of California San Francisco, San Francisco, California, United States

Fibroblast growth factor 23 (FGF23) is thought to be produced predominantly by osteocytes in bone and to exert a phosphate-regulating action in the kidneys. Its levels increase with development of chronic kidney disease and acute kidney injury (AKI) and are linked to morbidity and mortality. Recently, other tissues were reported to be additional sources of FGF23 in kidney injury or iron deficiency. However, it is unclear to what extent the extra-skeletal sources contribute to the baseline and the massively elevated serum FGF23 levels in AKI.


FGF23fl/fl mice carrying loxP sequences flanking exon 1 of Fgf23 gene were bred with Zp3-Cre and DMP1-Cre lines to produce global (FGF23-null) and osteocyte-specific FGF23 (OcyFGF23-KO) KO mice, respectively. AKI was induced after a single folic acid (FA) injection in adult male and female OcyFGF23-KO and control mice and circulating intact and c-terminal FGF23, PTH, and mineral levels as well as Fgf23 mRNA expression in various tissues were determined 24 hours after induction of AKI.


The FGF23-null mice recapitulated serum and skeletal phenotypes of the previously reported germ-line FGF23 KO mice, validating our gene KO strategy. Basal serum FGF23 and PTH levels in the OcyFGF23-KO mice were 39-50% and 48-67% lower (depending on sexes) compared to control mice, respectively. While serum cFGF23 levels were increased by AKI more robustly in control (6904±1272 pg/ml) vs OcyFGF23-KO mice (3178+836.1 pg/ml) (p<0.05), the fold-change over baseline value was similar between the 2 groups (35 in control vs 41 fold in KO mice, p=0.69). Accordingly, AKI induced higher PTH levels in control (2583±339.5 pg/ml) vs OcyFGF23-KO mice (1349±363.9 pg/ml, p<0.05), despite no difference in phosphate, calcium, and BUN levels between the two mouse groups after 24 hrs of AKI. As expected, FA did not increase FGF23 mRNA levels in the bone of OcyFGF23-KO mice, but raised FGF23 mRNA levels in their kidney and spleen by 5-10 fold.


We conclude that although the osteocytes contribute greatly to baseline FGF23 levels and to the increase of FGF23 in AKI, extra-skeletal tissues, particularly spleen and kidney, are also significant sources of FGF23 at physiological and injury states.


  • NIDDK Support