1ɑ, 25‐Dihydroxyvitamin D3 promotes osteogenesis by down‐regulating FGF23 in diabetic mice. Issue 8 (20th February 2021)

• Record Type: Journal Article
• Authors: Luo, Wenqiong; Jiang, Yixuan; Yi, Zumu; Wu, Yingying; Gong, Ping; Xiong, Yi
• Is Part Of: Journal of cellular and molecular medicine. Volume 25:Issue 8(2021)
• Page Start: 4148
• Page End: 4156
• Publication Date: 2021-02-20
• Subjects: 1ɑ, 25‐Dihydroxyvitamin D3(1, 25D) -- diabetes mellitus -- fibroblast growth factor 23 (FGF23) -- osteogenesis -- transcription factor Forkhead Box O1 (FOXO1); Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.16384
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 1ɑ, 25‐dihydroxyvitamin D3 (1, 25D) and fibroblast growth factor 23 (FGF23) play important roles in bone metabolism through mutual regulation. However, the underlying mechanism between 1, 25D and FGF23 in diabetes‐induced bone metabolism disorders has not yet been elucidated. In this study, we investigated the effect of 1, 25D on FGF23 under diabetic condition both in vitro and in vivo. The results showed that 1, 25D down‐regulated the expression of FGF23 in osteoblast significantly though a dose‐dependent manner in vitro within high glucose environment. Western blot and immunofluorescence analysis indicated that 1, 25D activated PI3K/Akt signalling through binding to vitamin D receptor (VDR), which inhibited the phosphorylation of the transcription factor Forkhead Box O1 (FOXO1). Decreased phosphorylation of FOXO1 down‐regulated the expression Dickkopf‐1 (DKK1), a well‐known inhibitor of Wnt signalling. In addition, we observed that 1, 25D remarkably ameliorated osteogenic phenotypic markers such as Ocn and Runx2 and rescued diabetes‐induced bone loss in vivo. Our results suggested that 1, 25D could promote osteogenesis though down‐regulating FOXO1/FGF23 in diabetes.