Vitamin D sterols increase FGF23 expression by stimulating osteoblast and osteocyte maturation in CKD bone

Bone
Renata C PereiraKatherine Wesseling-Perry

Abstract

Impaired osteoblast and osteocyte maturation contribute to mineralization defects and excess FGF23 expression in CKD bone. Vitamin D sterols decrease osteoid accumulation and increase FGF23 expression; these agents also increase osteoblast maturation in vitro but a link between changes in bone cell maturation, bone mineralization, and FGF23 expression in response to vitamin D sterols has not been established. We evaluated unmineralized osteoid accumulation, osteocyte maturity markers (FGF23: early osteocytes; sclerostin: late osteocytes), and osteocyte apoptosis in iliac crest of 11 pediatric dialysis patients before and after 8 months of doxercalciferol therapy. We then evaluated the effect of 1,25(OH)2vitamin D on in vitro maturation and mineralization of primary osteoblasts from dialysis patients. Unmineralized osteoid accumulation decreased while numbers of early (FGF23-expressing) increased in response to doxercalciferol. Osteocyte apoptosis was low but increased with doxercalciferol. Bone FGF23 expression correlated with numbers of early, FGF23-expressing, osteocytes (r = 0.83, p < 0.001). In vitro, 1,25(OH)2vitamin D increased expression of the mature osteoblast marker osteocalcin (BGLAP) but only very high (100 nM) conc...Continue Reading

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