期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 8, 页码 4148-4156出版社
WILEY
DOI: 10.1111/jcmm.16384
关键词
1a,25-Dihydroxyvitamin D3(1,25D); diabetes mellitus; fibroblast growth factor 23 (FGF23); osteogenesis; transcription factor Forkhead Box O1 (FOXO1)
资金
- Sichuan Science and Technology Program [2020JDRC0055]
- West China Hospital Basic and Applied Basic Research Foundation [RD--02--201913]
- China Postdoctoral Science Foundation [2019M653442]
The study found that 1,25D can promote bone metabolism under diabetes-induced conditions by regulating the FOXO1/FGF23 signaling pathway, leading to improved bone health and reduced bone loss in diabetic individuals.
1a,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.
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