The Increase in FGF23 Induced by Calcium Is Partially Dependent on Vitamin D Signaling

Background: Increased FGF23 levels are an early pathological feature in chronic kidney disease (CKD), causing increased cardiovascular risk. The regulation of FGF23 expression is complex and not completely understood. Thus, Ca has been shown to induce an increase in FGF23 expression, but whether that increase is mediated by simultaneous changes in parathyroid hormone (PTH) and/or vitamin D is not fully known.

Methods: Osteoblast-like cells (OLCs) from vitamin D receptor (VDR) and VDR mice were incubated with Ca for 18 h. Experimental hypercalcemia was induced by calcium gluconate injection in thyro-parathyroidectomized (T-PTX) VDR and VDR mice with constant PTH infusion.

Results: Inorganic Ca induced an increase in FGF23 gene and protein expression in osteoblast-like cells (OLCs), but the increase was blunted in cells lacking VDR. In T-PTX VDR and VDR mice with constant PTH levels, hypercalcemia induced an increase in FGF23 levels, but to a lower extent in animals lacking VDR. Similar results were observed in FGF23 expression in bone. Renal and bone 1α-hydroxylase expression was also modulated.

Conclusions: Our study demonstrates that Ca can increase FGF23 levels independently of vitamin D and PTH, but part of the physiological increase in FGF23 induced by Ca is mediated by vitamin D signaling.