External factors: | 1,25(OH)2D3 |
Aging type: | Prevent |
Aging characteristic: |
Category: | Chemical compounds |
Phenotype: | Osteoporosis |
Experiment: | SA-β-gal activity assay//Western blot |
Description: | Serum calcium and phosphorus levels were increased significantly in exogenous 1,25(OH)2D3-supplemented 18-month-old mice compared with vehicle-treated mice. In addition, BMD, trabecular bone volume, trabecular number and thickness, osteoblast number, MAR, and BFR were increased significantly ,whereas TRAP-positive osteoclastic number, the percentages of β-gal+, p16+, and IL-6+ osteocytes, and the mRNA levels of TNFα,IL-1α, IL-1β, IL-6, Mmp3, and p16 were all significantly decreased in exogenous 1,25(OH)2D3-supplemented 18-month-old mice compared with vehicle-treated mice. |
Regulatory pathway: | VDR-Ezh2-p16 |
R-EF-Pathway: | -- |
Official symbol(s): | VDR-EZH2-CDKN2A |
Pathway experiment: | Western blot//qRT-PCR//CHIP//Luciferase reporter assay |
Pathway description: | We found that 1,25(OH)2D3 increased the mRNA level of Ezh2 and down-regulated p16 and p19 expression at both protein and mRNA levels .The results of a ChIP-PCR assay demonstrated that the VDR could directly bind to the Ezh2 promoter at the predicted binding site. Luciferase reporter assays demonstrated that treatment of 1,25-(OH)2-D3 increased luciferase activity significantly in BM-MSCs transfected with an Ezh2-Luc plasmid, but failed to activate the mutant Luc reporter. |
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