Inhibition of PP2A enhances the osteogenic differentiation of human aortic valvular interstitial cells via ERK and p38 MAPK pathways

Objective. Parathyroid hormone (PTH) is considered to be essential during the tooth development. Stem cells from the apical papilla (SCAPs) are responsible for dentine formation. However, the interaction between PTH and SCAPs remains unclear. This study was aimed at investigating the effects of PTH on odonto/osteogenic differentiation capacity of SCAPs and elucidating the underlying molecular mechanisms. Materials and Methods. Here, SCAPs were isolated and identified in vitro. Effects of PTH on the proliferation of SCAPs were determined by Cell Counting Kit-8 (CCK-8), flow cytometry (FCM), and EdU. Alkaline phosphatase (ALP) activity, alizarin red staining, Western blot, and RT-PCR were carried out to detect the odonto/osteogenic differentiation of PTH-treated SCAPs as well as the participation of the MAPK signaling pathway. Results. An ALP activity assay determined that 10-8 mol/L PTH was the optimal concentration for the induction of SCAPs with no significant influence on the proliferation of SCAPs as indicated by CCK-8, FCM, and EdU. The expression of odonto/osteogenic markers was significantly upregulated in mRNA levels and protein levels. Moreover, intermittent treatment of PTH also increased phosphorylation of JNK and P38, and the differentiation was suppressed following the inhibition of JNK and P38 MAPK pathways. Conclusion. PTH can regulate the odonto/osteogenic differentiation of SCAPs via JNK and P38 MAPK pathways.

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Oxidized Low-Density Lipoprotein Promotes Osteoblastic Differentiation of Valvular Interstitial Cells through RAGE/MAPK

Cardiology ◽

10.1159/000369126 ◽

2014 ◽

Vol 130 (1) ◽

pp. 55-61 ◽

Cited By ~ 14

Author(s):

Fei Li ◽

Zhihong Zhao ◽

Zhejun Cai ◽

Nianguo Dong ◽

Yi Liu

Keyword(s):

Osteogenic Differentiation ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Interstitial Cells ◽

Osteoblastic Differentiation ◽

Mitogen Activated Protein Kinase ◽

Low Density ◽

Valvular Interstitial Cells ◽

Oxidized Low Density Lipoprotein

Objectives: We have previously shown that oxidized low-density lipoprotein (oxLDL) promotes the osteogenic differentiation of valvular interstitial cells (VICs) by inducing endoplasmic reticulum (ER) stress. We also demonstrated the detrimental role of the receptor for advanced glycation end products (RAGE) activation and signaling in the development and progression of aortic valve (AV) calcification. Here, we test the hypothesis that oxLDL may induce the osteoblastic differentiation of VICs via RAGE. Methods: Cultured porcine aortic VICs were used in an in vitro model. The VICs were incubated with oxLDL for analysis, with and without RAGE siRNA. Results: We found that oxLDL markedly increased the expression of RAGE, induced high levels of proinflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs. oxLDL also induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) MAPK. However, these effects were found to be markedly suppressed by siRNA silencing of RAGE. Conclusions: Our data provide evidence that RAGE mediates oxLDL-induced activation of p38 and JNK MAPK and the osteogenic differentiation of VICs.

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Role of myocardin-related transcription factors in myofibroblastic activation of valvular interstitial cells from aortic valves

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0032-1332652 ◽

2013 ◽

Vol 61 (S 01) ◽

Author(s):

W Witt ◽

P Büttner ◽

A Jannasch ◽

K Matschke ◽

T Waldow

Keyword(s):

Transcription Factors ◽

Interstitial Cells ◽

Valvular Interstitial Cells ◽

Aortic Valves

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LncRNA AFAP1-AS1 promotes M1 polarization of macrophages and osteogenic differentiation of valve interstitial cells

Journal of Physiology and Biochemistry ◽

10.1007/s13105-021-00821-0 ◽

2021 ◽

Author(s):

Welai He ◽

Hong Che ◽

Chaolong Jin ◽

Yanli Li ◽

Feng Li ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Interstitial Cells ◽

Valve Interstitial Cells ◽

M1 Polarization

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Heme-Mediated Activation of the Nrf2/HO-1 Axis Attenuates Calcification of Valve Interstitial Cells

Biomedicines ◽

10.3390/biomedicines9040427 ◽

2021 ◽

Vol 9 (4) ◽

pp. 427

Author(s):

Enikő Balogh ◽

Arpan Chowdhury ◽

Haneen Ababneh ◽

Dávid Máté Csiki ◽

Andrea Tóth ◽

...

Keyword(s):

Target Gene ◽

Interstitial Cells ◽

Protective Role ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Valvular Interstitial Cells ◽

Aortic Valves ◽

Antioxidant Genes ◽

Valve Interstitial Cells ◽

Nrf2 Target Gene

Calcific aortic valve stenosis (CAVS) is a heart disease characterized by the progressive fibro-calcific remodeling of the aortic valves, an actively regulated process with the involvement of the reactive oxygen species-mediated differentiation of valvular interstitial cells (VICs) into osteoblast-like cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of a variety of antioxidant genes, and plays a protective role in valve calcification. Heme oxygenase-1 (HO-1), an Nrf2-target gene, is upregulated in human calcified aortic valves. Therefore, we investigated the effect of Nrf2/HO-1 axis in VIC calcification. We induced osteogenic differentiation of human VICs with elevated phosphate and calcium-containing osteogenic medium (OM) in the presence of heme. Heme inhibited Ca deposition and OM-induced increase in alkaline phosphatase and osteocalcin (OCN) expression. Heme induced Nrf2 and HO-1 expression in VICs. Heme lost its anti-calcification potential when we blocked transcriptional activity Nrf2 or enzyme activity of HO-1. The heme catabolism products bilirubin, carbon monoxide, and iron, and also ferritin inhibited OM-induced Ca deposition and OCN expression in VICs. This study suggests that heme-mediated activation of the Nrf2/HO-1 pathway inhibits the calcification of VICs. The anti-calcification effect of heme is attributed to the end products of HO-1-catalyzed heme degradation and ferritin.

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