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Background and Aims Cardiovascular disease accounts for a major proportion of deaths among chronic kidney disease (CKD) patients. Fibroblast Growth Factor 23 (FGF23), a key regulator in phosphate homeostasis and mainly produced by osteocytes, is associated with CKD progression and cardiovascular mortality. FGF23 is involved in the development of left ventricular hypertrophy that can lead to congestive heart failure. Dysfunction of the heart causes tissue malperfusion, for instance in bones, inducing the hypoxia-inducible signaling pathway. Recently, the hypoxia-inducible factor-1α (HIF-1α) has been suggested as inducer of FGF23. Therefore, we investigated whether hypoxia in osteocytes induces FGF23 production mediated by the stabilization of HIFs. Method Human sarcoma osteogenic cells (SaOS2 cell line) and primary human osteocytes were cultured and exposed to hypoxic conditions (1% and 5% O2) and normoxic condition (20% O2) for 24 hours. qPCR was performed to investigate the expression of HIFs and FGF23 mRNA in these cells. HIFs protein expression was also evaluated by Western Blot analysis. Results Our data show that HIF-1α, and not HIF-2α, protein increases in SaOS2 cells and primary osteocytes under hypoxic conditions as compared to normoxic condition. In addition, we found that FGF23 mRNA expression is elevated in SaOS2 cells in these hypoxic conditions compared to normoxic condition (Fig.1). This increase was significant in SaOS2 cells exposed to 1% O2 (p &amp;lt;0.05). Preliminary data of primary osteocytes show that FGF23 mRNA is not expressed in hypoxic conditions compared with normoxic conditions (Fig.1). Conclusion HIF-1α protein was increased in both SaOS2 cells and primary osteocytes exposed to 1% O2. Hypoxic conditions upregulated FGF23 mRNA in SaOS2 cells. Taken together, these findings suggest that bone malperfusion upregulates FGF23 by stabilizing HIF-1α. This could then close a vicious circle where FGF23 induces cardiovascular disease, and circulatory failure upregulates FGF23.

MO057HYPOXIA AS INDUCER OF FIBROBLAST GROWTH FACTOR 23 IN OSTEOCYTES