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

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?

SUBMITTER: Pereira RC 

PROVIDER: S-EPMC6715148 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature