Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification

Liberman, Marcel; Johnson, Rebecca; Handy, Diane E.; Loscalzo, Joseph; Leopold, Jane A.

doi:10.1016/j.bbrc.2011.08.114

Cited by 104 publications

(83 citation statements)

References 29 publications

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“…S4). This is also in agreement with previous findings on the contribution of NOX to BMP2-stimulated osteoblast differentiation [8,37]. However, several open questions such as the nature of connection between ROS production and the activation of PARP1 as well as mediators of downstream signaling remain to be elucidated.…”

Section: Discussionsupporting

confidence: 92%

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

Robaszkiewicz

Valkó

Kovács

et al. 2014

Free Radical Biology and Medicine

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a b s t r a c tOsteogenic differentiation is a multistep process regulated by a diverse set of morphogenic and transcription factors. Previously we identified endogenous hydrogen peroxide-induced poly(ADP-ribose) polymerase-1 (PARP1) activation as a mediator of osteodifferentiation and associated cell death. Here we set out to investigate whether or not activation of PARP1 is dependent on DNA breaks and how PARP1 mediates cell death during osteodifferentiation of mesenchymal stem cells and SAOS-2 cells. Here we show that the MAP kinases p38, JNK, and ERK1/2 become activated during the differentiation process. However, only p38 activation depended both on hydrogen peroxide production and on PARP1 activation as the hydrogen peroxide decomposing enzyme catalase, the PARP inhibitor PJ34, and the silencing of PARP1 suppressed p38 activation. Inhibition of p38 suppressed cell death and inhibited osteogenic differentiation (calcium deposition, alkaline phosphatase activity, and marker gene expression) providing further support for the close coupling of osteodifferentiation and cell death. Metabolic collapse appears to be central in the hydrogen peroxide-PARP1-p38 pathway as silencing PARP1 or inhibition of p38 prevented differentiation-associated loss of cellular NAD, inhibition of mitochondrial respiration, and glycolytic activity. We also provide evidence that endogenous hydrogen peroxide produced by the differentiating cells is sufficient to cause detectable DNA breakage. Moreover, p38 translocates from the cytoplasm to the nucleus where it interacts and colocalizes with PARP1 as detected by immunoprecipitation and immunofluorescence, respectively. In summary, hydrogen peroxide-induced PARP1 activation leads to p38 activation and this pathway is required both for the successful completion of the differentiation process and for the associated cell death.

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Section: Discussionsupporting

confidence: 92%

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

Robaszkiewicz

Valkó

Kovács

et al. 2014

Free Radical Biology and Medicine

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“…[25][26][27][28] In endothelial cells (ECs), XBP1 splicing plays diverse roles, including cell proliferation, 26 autophagy response, 29 and apoptosis. 30 In SMCs, bone morphogenetic protein-2 was reported to activate XBP1 splicing, 31 but the exact role of XBP1 in SMCs still remains unclear. In this study, we demonstrated that XBP1 splicing is crucial in PDGF-BB-induced SMC proliferation and contributes to neointima formation after vascular injury.…”

mentioning

confidence: 99%

XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling

Zeng

Yang

et al. 2015

ATVB

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Objective-Smooth muscle cell (SMC) migration and proliferation play an essential role in neointimal formation after vascular injury. In this study, we intended to investigate whether the X-box-binding protein 1 (XBP1) was involved in these processes. Approach and Results-In vivo studies on femoral artery injury models revealed that vascular injury triggered an immediate upregulation of XBP1 expression and splicing in vascular SMCs and that XBP1 deficiency in SMCs significantly abrogated neointimal formation in the injured vessels. In vitro studies indicated that platelet-derived growth factor-BB triggered XBP1 splicing in SMCs via the interaction between platelet-derived growth factor receptor β and the inositolrequiring enzyme 1α. The spliced XBP1 (XBP1s) increased SMC migration via PI3K/Akt activation and proliferation via downregulating calponin h1 (CNN1). XBP1s directed the transcription of mir-1274B that targeted CNN1 mRNA degradation. Proteomic analysis of culture media revealed that XBP1s decreased transforming growth factor (TGF)-β family proteins secretion via transcriptional suppression. TGF-β3 but not TGF-β1 or TGF-β2 attenuated XBP1s-induced CNN1 decrease and SMC proliferation. Conclusions-This study demonstrates for the first time that XBP1 is crucial for SMC proliferation via modulating the platelet-derived growth factor/TGF-β pathways, leading to neointimal formation. under stress conditions. [21][22][23] Under ER stress conditions, XBP1 mRNA undergoes unconventional splicing through an ER-resident kinase that possesses ribonuclease activity, the inositol-requiring enzyme 1 α (IRE1α). 24 Our recent studies and reports from other groups showed that physiological stimuli such as vascular endothelial cell growth factor could trigger XBP1 splicing in an ER stress response-independent manner. [25][26][27][28] In endothelial cells (ECs), XBP1 splicing plays diverse roles, including cell proliferation, 26 autophagy response, 29 and apoptosis. 30 In SMCs, bone morphogenetic protein-2 was reported to activate XBP1 splicing, 31 but the exact role of XBP1 in SMCs still remains unclear. In this study, we demonstrated that XBP1 splicing is crucial in PDGF-BB-induced SMC proliferation and contributes to neointima formation after vascular injury. Materials and MethodsMaterials and Methods are available in the online-only Data Supplement. Results Vascular Injury Increased XBP1 Expression and SplicingIn response to vascular injury, vascular SMCs will be activated undergoing migration, proliferation, and apoptosis. 32 To test whether XBP1 was involved in SMC activation, femoral artery injury model was introduced into the right side of C57Bl/6 mice. The injured vessels were harvested at day 1, and day 3 post surgery, whereas the left uninjured vessels were collected as control. Double immunofluorescence staining with anti-α SMC actin and antispliced XBP1 (XBP1s) or unspliced XBP1 (XBP1u) antibodies were performed on the cryo-sections. As shown in Figure 1A, low levels of XBP1s and XBP1u were detected in the uninjure...

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“…[8][9][10] Recent reports have shown that ER stress occurs during osteogenic differentiation. [17][18][19][20][21] ER stressinduced apoptosis of osteoblasts has also been implicated in the pathogenesis of osteoporosis. [22][23][24][25][26] Our study found that the MC3T3-E1 cells, the mouse calvaria osteoblasts, were led into the decrease of cellular viability in response to ER stress.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have shown that several osteogenic cytokines, such as bone morphogenetic protein-2 (BMP-2) could induce osteoblasts ER stress during osteogenic differentiation. 17,18 Some ER stress-associated proteins have a significant role in bone formation. For example, old astrocyte specifically induced substance (OASIS), an ER stress transducer, has been implicated to be involved in bone formation through the transcription of COL1A1 and the secretion of bone matrix proteins.…”

mentioning

confidence: 99%

17β-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I-dependent Grp78 induction in osteoblasts

Guo

Sun

et al. 2014

Laboratory Investigation

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Although many studies have suggested that estrogen prevents postmenopausal bone loss partially due to its anti-apoptosis effects in osteoblasts, the underlying mechanism has not been fully elucidated. In the present study, we found that 17b-estradiol (17b-E 2 ), one of the primary estrogens, inhibited endoplasmic reticulum (ER) stress-induced apoptosis in MC3T3-E1 cells and primary osteoblasts. Interestingly, 17b-E 2 -promoted Grp78 induction, but not CHOP induction in response to ER stress. We further confirmed that Grp78-specific siRNA reversed the inhibition of 17b-E 2 on ER stress-induced apoptosis by activating caspase-12 and caspase-3. Moreover, we found that 17b-E 2 markedly increased the phosphorylated TFII-I levels and nuclear localization of TFII-I in ER stress conditions. 17b-E 2 stimulated Grp78 promoter activity in a dose-dependent manner in the presence of TFII-I and enhanced the binding of TFII-I to the Grp78 promoter. In addition, 17b-E 2 notably increased phosphorylated ERK1/2 levels and Ras kinase activity in MC3T3-E1 cells. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked 17b-E 2 -induced TFII-I phosphorylation and Grp78 expression in response to ER stress. Together, 17b-E 2 protected MC3T3-E1 cells against ER stress-induced apoptosis by promoting Ras-ERK1/2-TFII-I signaling pathway-dependent Grp78 induction.Laboratory Investigation (2014) 94, 906-916;

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Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification

Cited by 104 publications

References 29 publications

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

The role of p38 signaling and poly(ADP-ribosyl)ation-induced metabolic collapse in the osteogenic differentiation-coupled cell death pathway

XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling

17β-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I-dependent Grp78 induction in osteoblasts

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