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Vitamin C epigenetically controls osteogenesis and bone mineralization.

ABSTRACT: Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transcriptional activity. Vitamin C regulates histone demethylation (H3K9me3 and H3K27me3) and promotes TET-mediated 5hmC DNA hydroxymethylation at promoters, enhancers and super-enhancers near bone-specific genes. This epigenetic circuit licenses osteoblastogenesis by permitting the expression of all major pro-osteogenic genes. Osteogenic cell differentiation is strictly and continuously dependent on Vitamin C, whereas Vitamin C is dispensable for adipogenesis. Importantly, deletion of 5hmC-writers, Tet1 and Tet2, in Vitamin C-sufficient murine bone causes severe skeletal defects which mimic bone phenotypes of Vitamin C-insufficient Gulo knockout mice, a model of Vitamin C deficiency and scurvy. Thus, Vitamin C's epigenetic functions are central to osteoblastogenesis and bone formation and may be leveraged to prevent common bone-degenerating conditions.

SUBMITTER: Thaler R

PROVIDER: S-EPMC9537512 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Vitamin C epigenetically controls osteogenesis and bone mineralization.

Thaler Roman R Khani Farzaneh F Sturmlechner Ines I Dehghani Sharareh S SS Denbeigh Janet M JM Zhou Xianhu X Pichurin Oksana O Dudakovic Amel A Jerez Sofia S SS Zhong Jian J Lee Jeong-Heon JH Natarajan Ramesh R Kalajzic Ivo I Jiang Yong-Hui YH Deyle David R DR Paschalis Eleftherios P EP Misof Barbara M BM Ordog Tamas T van Wijnen Andre J AJ

Nature communications 20221006 1

Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transcriptional activity. Vitamin C regulates histone demethylation (H3K9me3 and H3K27me3) and promotes TET-mediated 5hmC DNA hydroxymethylation at promoter ...[more]

PMID: 36202795

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Vitamin C epigenetically controls osteogenesis and bone mineralization.

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Vitamin C epigenetically controls osteogenesis and bone mineralization.

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