Vitamin D–regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification

Nguyen-Yamamoto, Loan; Tanaka, Kenichiro; St‐Arnaud, René; Goltzman, David

doi:10.1172/jci.insight.126467

Cited by 36 publications

(29 citation statements)

References 65 publications

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“…Vitamin D can regulate a variety of important pathways [34][35][36][37] . Among these, the NF-κB pathway plays an important role in the regulation of cisplatin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Huang

Zhang

et al. 2019

Cell Death Dis

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Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.

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“…Vitamin D can regulate a variety of important pathways [34][35][36][37] . Among these, the NF-κB pathway plays an important role in the regulation of cisplatin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Huang

Zhang

et al. 2019

Cell Death Dis

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“…Fu et al found that 1,25(OH)2D suppressed BMP2 activity in the bone marrow MSCs by binding the BMP2 promoting region [143]. Goltzman et al also provided in vivo evidence that the vitamin D that originated from the osteocyte directly decreased the BMP2 release into serum and then mitigated the extraskeletal calcification [144]. Human marrow-derived MSCs (marrow stromal cells, hMSCs) give rise to osteoblasts, and their differentiation is stimulated by 1α,25(OH)2D, although hMSCs can also synthesize 1α,25(OH)2D.…”

Section: The Role Of Vitamin D and Mscs/pericytes In Vascular Calcifimentioning

confidence: 99%

The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification

Hou

Zheng

et al. 2020

IJMS

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Vascular calcification, which involves the deposition of calcifying particles within the arterial wall, is mediated by atherosclerosis, vascular smooth muscle cell osteoblastic changes, adventitial mesenchymal stem cell osteoblastic differentiation, and insufficiency of the calcification inhibitors. Recent observations implied a role for mesenchymal stem cells and endothelial progenitor cells in vascular calcification. Mesenchymal stem cells reside in the bone marrow and the adventitial layer of arteries. Endothelial progenitor cells that originate from the bone marrow are an important mechanism for repairing injured endothelial cells. Mesenchymal stem cells may differentiate osteogenically by inflammation or by specific stimuli, which can activate calcification. However, the bioactive substances secreted from mesenchymal stem cells have been shown to mitigate vascular calcification by suppressing inflammation, bone morphogenetic protein 2, and the Wingless-INT signal. Vitamin D deficiency may contribute to vascular calcification. Vitamin D supplement has been used to modulate the osteoblastic differentiation of mesenchymal stem cells and to lessen vascular injury by stimulating adhesion and migration of endothelial progenitor cells. This narrative review clarifies the role of mesenchymal stem cells and the possible role of vitamin D in the mechanisms of vascular calcification.

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“…In vitro, sclerostin was expressed in the calcification process of vascular smooth muscle cells [74]. Recently, Nguyen-Yamamoto et al showed in a mice model study that sclerostin protected the organism from VC by suppressing BMP2 production [82].…”

Section: Dickkopf Proteins (Dkk)mentioning

confidence: 99%

Pathophysiological and Genetic Aspects of Vascular Calcification

Guzman

Guzmán

Lopes

2020

Cardiology Research and Practice

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Recent evidence suggests that vascular calcification is an independent cardiovascular risk factor (CRF) of morbidity and mortality. New studies point out the existence of a complex physiopathological mechanism that involves inflammation, oxidation, the release of chemical mediators, and genetic factors that promote the osteochondrogenic differentiation of vascular smooth muscle cells (VSMC). This review will evaluate the main mechanisms involved in the pathophysiology and genetics modulation of the process of vascular calcification. Objective. A systematic review of the pathophysiology factors involved in vascular calcification and its genetic influence was performed. Methods. A systematic review was conducted in the Medline and PubMed databases and were searched for studies concerning vascular calcification using the keywords and studies published until 2020/01 in English. Inclusion Criteria. Studies in vitro, animal models, and humans. These include cohort (both retrospective and prospective cohort studies), case-control, cross-sectional, and systematic reviews. Exclusion Criteria. Studies before 2003 of the existing literature.

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Vitamin D–regulated osteocytic sclerostin and BMP2 modulate uremic extraskeletal calcification

Cited by 36 publications

References 65 publications

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification

Pathophysiological and Genetic Aspects of Vascular Calcification

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