Vitamin C epigenetically controls osteogenesis and bone mineralization

Thaler, Roman; Khani, Farzaneh; Sturmlechner, Ines; Dehghani, Sharareh S.; Denbeigh, Janet M.; Zhou, Xianhu; Pichurin, Oksana; Dudakovic, Amel; Jerez, Sofía; Zhong, Jian; Lee, Jeong‐Heon; Natarajan, Ramesh; Kalajzić, Ivo; Jiang, Yong‐Hui; Deyle, David R.; Paschalis, Eleftherios P.; Misof, Barbara M.; Ördög, Tamás; Wijnen, André J. van

doi:10.1038/s41467-022-32915-8

Cited by 38 publications

(31 citation statements)

References 78 publications

(98 reference statements)

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“…Intriguingly, recent research indicates that inhibiting prolyl-hydroxylase activity using its specific inhibitor 1,4-DPCA does not stop the expression of the mature osteoblastic gene, suggesting that osteogenic transcriptional program is independent of collagen synthesis during osteoblastogenesis. (38) On the other hand, several studies indicated that the endogenous CaMKII activity plays an important role in cartilage hypertrophy via modulating Col10a1 biosynthesis in hypertrophic chondrocytes. (39)(40)(41) In this study, we demonstrated that MAP promoted Col1a1 biosynthesis in SSPCs by activating the CaMKIIα.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling

Xie

Bao

Wang

et al. 2023

J of Bone & Mineral Res

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Dysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs) in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified calcium/calmodulin‐dependent serine/threonine kinase IIα (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (extracellular regulated kinase 1/2) and CREB (cAMP‐response element binding protein) as well as an elevation of C‐FOS expression. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C‐FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

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Section: Discussionmentioning

confidence: 99%

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling

Xie

Bao

Wang

et al. 2023

J of Bone & Mineral Res

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“…In the Gulo -/- mice model, where mice can only consume Vitamin C through exogenous supplementation, five weeks of Vitamin C deprivation elevated H3K9me3 and H3K27me3 marks in bone tissue. Furthermore, the knockdown of H3K9me3 demethylases KDM4A and KDM4B significantly downregulated the osteogenic capacity of MSCs ( 137 ).…”

Section: Epigenetic Control Of Mscs In Bone Regenerationmentioning

confidence: 99%

Epigenetic control of mesenchymal stem cells orchestrates bone regeneration

2023

Front. Endocrinol.

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Recent studies have revealed the vital role of MSCs in bone regeneration. In both self-healing bone regeneration processes and biomaterial-induced healing of bone defects beyond the critical size, MSCs show several functions, including osteogenic differentiation and thus providing seed cells. However, adverse factors such as drug intake and body senescence can significantly affect the functions of MSCs in bone regeneration. Currently, several modalities have been developed to regulate MSCs’ phenotype and promote the bone regeneration process. Epigenetic regulation has received much attention because of its heritable nature. Indeed, epigenetic regulation of MSCs is involved in the pathogenesis of a variety of disorders of bone metabolism. Moreover, studies using epigenetic regulation to treat diseases are also being reported. At the same time, the effects of epigenetic regulation on MSCs are yet to be fully understood. This review focuses on recent advances in the effects of epigenetic regulation on osteogenic differentiation, proliferation, and cellular senescence in MSCs. We intend to illustrate how epigenetic regulation of MSCs orchestrates the process of bone regeneration.

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“…Intracellular biosynthetic and metabolic systems are very diverse to maintain normal physiological requirements. , Amino acid metabolism, citric acid metabolism, glycolytic metabolism, and urea metabolism cycles provide the basis for the synthesis of organic small molecules and organic polymers. − Intracellular or extracellular biomineralization systems provide the chemical basis for the synthesis of inorganic nanomaterials, such as physiological mineralization and pathological mineralization. − The multidimensional structure of proteins is the site of nucleation for biomineralization of inorganic nanomaterials, or reduced biomolecules provide the chemical energy for biochemical synthesis and ultimately the formation of nanomaterials with specific functions. , This hints that the biosynthesis system may be an outstanding reactor to synthesize nanoprobes that can be used for chemical biomedical imaging.…”

Section: Biosynthesis Systemsmentioning

confidence: 99%

Tunable Nanomaterials of Intracellular Crystallization for In Situ Biolabeling and Biomedical Imaging

Liu

Jiang

Liu

et al. 2023

Chemical & Biomedical Imaging

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Intracellular biosynthetic nanomaterials offer tremendous opportunities for chemical biomedical imaging. A wide range of biologically active tissues are available for biosynthesis, including cells, bacteria, plants, and viruses. Nanomaterials synthesized by intracellular biomineralization with outstanding biosafety and optical properties attract unique attention. Herein, an overview of biosynthetic tunable nanomaterials within active biological tissues for chemical biomedical imaging is presented. The synthetic mechanisms and nanostructures of biosynthetic nanomaterials are summarized from the perspective of different active organisms. The ability of biosynthesis is commonly used for green synthesis of metal nanoparticles compared to those synthesized by physical or chemical methods. The tunable characteristics of these nanoparticles make it possible to utilize them as fluorescence imaging, surface-enhanced Raman spectral mapping, nuclear magnetic resonance imaging, and other biomedical photonics tools. Importantly, current issues, insights, and future tendencies of development are presented based on current biosynthetic optical nanomaterials for chemical biomedical imaging. This paper provides the summary of biosynthetic optical nanomaterials and a critical assessment of potential biomedical imaging applications in this emerging field, laying the foundation for future studies.

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Vitamin C epigenetically controls osteogenesis and bone mineralization

Cited by 38 publications

References 78 publications

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling

Epigenetic control of mesenchymal stem cells orchestrates bone regeneration

Tunable Nanomaterials of Intracellular Crystallization for In Situ Biolabeling and Biomedical Imaging

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