Hdac9 inhibits medial artery calcification through down-regulation of Osterix

He, Pengcheng; Yu, Hongjiao; Jiang, Lei; Chen, Ziying; Wang, Siying; MacRae, Vicky; Fu, Xiaodong; Zhu, Dongxing

doi:10.1016/j.vph.2020.106775

Cited by 12 publications

(14 citation statements)

References 35 publications

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“…First of all, we validated the vitamin D-induced mouse vascular calcification model in vivo . In accordance with the previous study ( He et al, 2020 ), vitamin D injection increased calcium deposition in murine aorta, as determined by alizarin red staining ( Figures 1A–C ). In addition, the critical regulators of osteogenic differentiation, such as Runx2 and Bmp2 , were significantly upregulated in calcified aortic tissues following vitamin D treatment at day 7, while the smooth muscle contractile marker, SMA, was significantly downregulated ( Figure 1D ).…”

Section: Resultssupporting

confidence: 92%

“…The primary mouse VSMCs were isolated as described in the previous study ( He et al, 2020 ). Briefly, the descending aorta was isolated from the 6-week-old male mice.…”

Section: Methodsmentioning

confidence: 99%

“…The induction of murine vascular calcification was performed as previously described ( He et al, 2020 ). Briefly, 6-week-old C57BL/6 male mice were given, subcutaneously injected of 5 × 10 5 IU/kg vD3 or vehicle once a day for 3 days, and sacrificed at 7 days after injection.…”

Section: Methodsmentioning

confidence: 99%

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CCAAT/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification

et al. 2022

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AimsVascular calcification is a common clinical complication of chronic kidney disease (CKD), atherosclerosis (AS), and diabetes, which is associated with increased cardiovascular morbidity and mortality in patients. The transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteochondrogenic phenotype is a crucial step during vascular calcification. The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) plays an important role in regulating cell proliferation and differentiation, but whether it regulates the calcification of arteries and VSMCs remains unclear. Therefore, this study aims to understand the role of C/EBPα in the regulation of vascular calcification.Methods and ResultsBoth mRNA and protein expression levels of C/EBPα were significantly increased in calcified arteries from mice treated with a high dose of vitamin D3 (vD3). Upregulation of C/EBPα was also observed in the high phosphate- and calcium-induced VSMC calcification process. The siRNA-mediated knockdown of C/EBPα significantly attenuated VSMC calcification in vitro. Moreover, C/EBPα depletion in VSMCs significantly reduced the mRNA expression of the osteochondrogenic genes, e.g., sex-determining region Y-box 9 (Sox9). C/EBPα overexpression can induce SOX9 overexpression. Similar changes in the protein expression of SOX9 were also observed in VSMCs after C/EBPα depletion or overexpression. In addition, silencing of Sox9 expression significantly inhibited the phosphate- and calcium-induced VSMC calcification in vitro.ConclusionFindings in this study indicate that C/EBPα is a key regulator of the osteochondrogenic transdifferentiation of VSMCs and vascular calcification, which may represent a novel therapeutic target for vascular calcification.

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Section: Resultssupporting

confidence: 92%

“…The primary mouse VSMCs were isolated as described in the previous study ( He et al, 2020 ). Briefly, the descending aorta was isolated from the 6-week-old male mice.…”

Section: Methodsmentioning

confidence: 99%

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CCAAT/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification

et al. 2022

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“…After the knockdown of the histone deacetylase Hdac9, the expression of Osx mRNA remained unchanged while the protein expression level was significantly enhanced and then resulted in the enhancement of VSMCs calcification in vitro . This process may be mediated by acetylation of Osx ( He et al, 2020 ). It has been confirmed that both endogenous and exogenous Osx protein can be acetylated.…”

Section: Post-translational Modifications Are Important For Osx Activmentioning

confidence: 99%

Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation

Liu

Wang

et al. 2020

Front. Cell Dev. Biol.

145

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With increasing life expectations, more and more patients suffer from fractures either induced by intensive sports or other bone-related diseases. The balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption is the basis for maintaining bone health. Osterix (Osx) has long been known to be an essential transcription factor for the osteoblast differentiation and bone mineralization. Emerging evidence suggests that Osx not only plays an important role in intramembranous bone formation, but also affects endochondral ossification by participating in the terminal cartilage differentiation. Given its essentiality in skeletal development and bone formation, Osx has become a new research hotspot in recent years. In this review, we focus on the progress of Osx’s function and its regulation in osteoblast differentiation and bone mass. And the potential role of Osx in developing new therapeutic strategies for osteolytic diseases was discussed.

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“…The animal model with soft tissue calci cation was constructed by using Vitamin D3 as previously described (18). A total of 30 female Kunming mice were divided into ve groups: control group (without any treatment), Vitamin D3 group, Vitamin D3 + Exosome group (the exosomes were extracted from general VSMCs), Vitamin D3 + miR-151-3p mimic Exosome group (the exosomes were extracted from miR-151-3p mimics transfected VSMCs), and Vitamin D3 + miR-151-3p inhibitor Exosome group (the exosomes were extracted from miR-151-3p inhibitor transfected VSMCs).…”

Section: Animal Modelmentioning

confidence: 99%

Exosomal miR-151-3p Induces Calcium Deposition in Vascular Smooth Muscle Cells by Inhibiting Atg5

Chen

Zhang

Jin-yin

et al. 2021

Preprint

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Background: Calcium deposition in vascular smooth muscle cells (VSMCs) can lead to the rigidity of the vasculature and an increase of risk in cardiac events. This study aimed to explore the role of exosomal microRNA-151-3p (miR-151-3p) in the regulation of VSMC calcification. Methods: A cellular calcification model was established using the mouse primary aortic VSMCs by β-glycerophosphate treatment. The calcium deposition was evaluated by Alizarin Red staining. The expression of miR-151-3p in exosomes was evaluated by qRT-PCR. The relationship between miR-151-3p and Atg5 was determined by bioinformatics analysis and dual-luciferase gene reporter assay. The exosome derived from mouse VSMCs transfected with miR-151-3p mimics/inhibitor were isolated and used to stimulate VSMCs. The expression of Atg5, α-SMA, OPN, Runx2 and BMP2 was evaluated by western blot. An animal model was established to investigate the role of miR-151-3p in exosomes.Results: MiR-151-3p was significantly upregulated in the exosomes of VSMCs treated with β-glycerophosphate. Exosomes derived from calcific VSMCs increased the calcium deposition of general VSMCs without any treatment. Exosomes derived from miR-151-3p mimics transfected VSMCs increased the expression of Runx2 and BMP2, while reduced the expression of α-SMA and OPN in general VSMCs. and exosomes derived from miR-151-3p inhibitor transfected VSMCs reversed these effects in vitro. Meanwhile, miR-151-3p served as a ceRNA of Atg5 by directly binding to the 3'UTR of Atg5. Moreover, the expression of α-SMA, OPN, Runx2 and BMP2 in vivo was consistent with the results in VSMCs in vitro.Conclusion: Our study revealed that miR-151-3p in VSMCs-derived exosomes might induce calcium deposition through regulating Atg5 expression, suggesting that miR-151-3p might be a potential biomarker for vascular calcification.

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Hdac9 inhibits medial artery calcification through down-regulation of Osterix

Cited by 12 publications

References 35 publications

CCAAT/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification

CCAAT/Enhancer-Binding Protein Alpha Is a Novel Regulator of Vascular Smooth Muscle Cell Osteochondrogenic Transition and Vascular Calcification

Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation

Exosomal miR-151-3p Induces Calcium Deposition in Vascular Smooth Muscle Cells by Inhibiting Atg5

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