1,25-Dihydroxyvitamin D protects against age-related osteoporosis by a novel VDR-Ezh2-p16 signal axis.

ABSTRACT: To determine whether 1,25-dihydroxyvitamin D (1,25(OH)₂ D) can exert an anti-osteoporosis role through anti-aging mechanisms, we analyzed the bone phenotype of mice with 1,25(OH)₂ D deficiency due to deletion of the enzyme, 25-hydroxyvitamin D 1α-hydroxylase, while on a rescue diet. 1,25(OH)₂ D deficiency accelerated age-related bone loss by activating the p16/p19 senescence signaling pathway, inhibiting osteoblastic bone formation, and stimulating osteoclastic bone resorption, osteocyte senescence, and senescence-associated secretory phenotype (SASP). Supplementation of exogenous 1,25(OH)₂ D₃ corrected the osteoporotic phenotype caused by 1,25(OH)₂ D deficiency or natural aging by inhibiting the p16/p19 pathway. The prolife

SUBMITTER: Yang R 

PROVIDER: S-EPMC6996957 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature