RAGE-dependent mitochondria pathway: a novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products.

Abstract:

:Advanced glycation end products (AGEs) can stimulate osteoblast apoptosis and have a critical role in the pathophysiology of diabetic osteoporosis. Mitochondrial abnormalities are closely related to osteoblast dysfunction. However, it remains unclear whether mitochondrial abnormalities are involved in AGE-induced osteoblastic cell apoptosis. Silibinin, a major flavonolignan compound of silimarin, has strong antioxidant and mitochondria-protective properties. In the present study, we explored the possible mitochondrial mechanisms underlying AGE-induced apoptosis of osteoblastic cells and the effect of silibinin on osteoblastic cell apoptosis. We demonstrated that mitochondrial abnormalities largely contributed to AGE-induced apoptosis of osteoblastic cells, as evidenced by enhanced mitochondrial oxidative stress, conspicuous reduction in mitochondrial membrane potential and adenosine triphosphate production, abnormal mitochondrial morphology, and altered mitochondrial dynamics. These AGE-induced mitochondrial abnormalities were mainly mediated by the receptor of AGEs (RAGE). In addition, we found that silibinin directly downregulated the expression of RAGE and modulated RAGE-mediated mitochondrial pathways, thereby preventing AGE-induced apoptosis of osteoblastic cells. This study not only provides a new insight into the mitochondrial mechanisms underlying AGE-induced osteoblastic cell apoptosis, but also lays a foundation for the clinical use of silibinin for the prevention or treatment of diabetic osteoporosis.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Mao YX,Cai WJ,Sun XY,Dai PP,Li XM,Wang Q,Huang XL,He B,Wang PP,Wu G,Ma JF,Huang SB

doi

10.1038/s41419-018-0718-3

subject

Has Abstract

pub_date

2018-06-04 00:00:00

pages

674

issue

6

issn

2041-4889

pii

10.1038/s41419-018-0718-3

journal_volume

9

pub_type

杂志文章
  • MiR34 inhibition induces human heart progenitor proliferation.

    abstract::MiR34 involvement in myocardial injury repair and ageing has been well documented in mouse model. Our aim was to establish whether the inhibition of miR34 expression through locked nucleic acid (LNA) could be used as a pharmacological intervention to enhance human heart repair. Cardiac progenitor cells were obtained b...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0400-9

    authors: Iannolo G,Sciuto MR,Raffa GM,Pilato M,Conaldi PG

    更新日期:2018-03-06 00:00:00

  • CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival.

    abstract::Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repress...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2010.10

    authors: Nicolai J,Burbassi S,Rubin J,Meucci O

    更新日期:2010-04-01 00:00:00

  • Arginase 2 deficiency reduces hyperoxia-mediated retinal neurodegeneration through the regulation of polyamine metabolism.

    abstract::Hyperoxia treatment has been known to induce neuronal and glial death in the developing central nervous system. Retinopathy of prematurity (ROP) is a devastating disease in premature infants and a major cause of childhood vision impairment. Studies indicate that, in addition to vascular injury, retinal neurons are als...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.23

    authors: Narayanan SP,Xu Z,Putluri N,Sreekumar A,Lemtalsi T,Caldwell RW,Caldwell RB

    更新日期:2014-02-20 00:00:00

  • c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of 6 months despite current therapies. NF-κB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and death receptor-induced apoptosis, bu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.417

    authors: Geismann C,Grohmann F,Sebens S,Wirths G,Dreher A,Häsler R,Rosenstiel P,Hauser C,Egberts JH,Trauzold A,Schneider G,Sipos B,Zeissig S,Schreiber S,Schäfer H,Arlt A

    更新日期:2014-10-09 00:00:00

  • MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.

    abstract::MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue usi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03306-y

    authors: Li Z,Zhao S,Zhu S,Fan Y

    更新日期:2021-01-04 00:00:00

  • Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation.

    abstract::Psoriasis is an autoimmune skin disease, where chronic immune responses due to exaggerated cytokine signaling, abnormal differentiation, and evasion of keratinocytes apoptosis plays a crucial role in mediating abnormal keratinocytes hyperproliferation. From the therapeutic perspective, the molecules with strong anti-p...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2212-y

    authors: Thatikonda S,Pooladanda V,Sigalapalli DK,Godugu C

    更新日期:2020-01-10 00:00:00

  • Long non-coding RNA H19 confers 5-Fu resistance in colorectal cancer by promoting SIRT1-mediated autophagy.

    abstract::Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer (CRC) patients. The role of the differentially expressed lncRNAs in 5-Fluorouracil chemoresistance has not fully explained. Here, we observed lncRNA H19 was associated with the 5-Fu resistance in CRC. Quantitative analysis in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1187-4

    authors: Wang M,Han D,Yuan Z,Hu H,Zhao Z,Yang R,Jin Y,Zou C,Chen Y,Wang G,Gao X,Wang X

    更新日期:2018-11-19 00:00:00

  • Pigment epithelium-derived factor hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina.

    abstract::Calcium ions play a critical role in neuronal cell death. Pigment epithelium-derived factor (PEDF) is a promising neuroprotective protein for photoreceptor cells but the mechanisms mediating its effects against retinal degeneration are still not well characterized. We addressed this question in the rd1 degenerating mo...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0613-y

    authors: Comitato A,Subramanian P,Turchiano G,Montanari M,Becerra SP,Marigo V

    更新日期:2018-05-01 00:00:00

  • Mitochondrial ferritin protects the murine myocardium from acute exhaustive exercise injury.

    abstract::Mitochondrial ferritin (FtMt) is a mitochondrially localized protein possessing ferroxidase activity and the ability to store iron. FtMt overexpression in cultured cells protects against oxidative damage by sequestering redox-active, intracellular iron. Here, we found that acute exhaustive exercise significantly incre...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.372

    authors: Wu W,Chang S,Wu Q,Xu Z,Wang P,Li Y,Yu P,Gao G,Shi Z,Duan X,Chang YZ

    更新日期:2016-11-17 00:00:00

  • MiR-422a regulates cellular metabolism and malignancy by targeting pyruvate dehydrogenase kinase 2 in gastric cancer.

    abstract::Increasing evidence indicates that dysregulation of microRNAs (miRNAs) plays a crucial role in human malignancies. Here, we showed that microRNA-422a (miR-422a) expression was dramatically downregulated in gastric cancer (GC) samples and cell lines compared with normal controls, and that its expression level was inver...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0564-3

    authors: He Z,Li Z,Zhang X,Yin K,Wang W,Xu Z,Li B,Zhang L,Xu J,Sun G,Wang L,Li Q,Huang X,Zhang L,Zhang D,Xu H,Xu Z

    更新日期:2018-05-01 00:00:00

  • 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.

    abstract::4-hydroxyphenylpyruvate dioxygenase (HPD) is an important modifier of tyrosine metabolism. However, the precise contribution of HPD to cancer metabolism and tumorigenesis remains unclear. In this study, we found that HPD was highly expressed in lung cancer and its higher expression correlated with poor prognosis in lu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1756-1

    authors: Shan C,Lu Z,Li Z,Sheng H,Fan J,Qi Q,Liu S,Zhang S

    更新日期:2019-07-08 00:00:00

  • Wnt signaling induces radioresistance through upregulating HMGB1 in esophageal squamous cell carcinoma.

    abstract::Although many articles have uncovered that Wnt signaling is involved in radioresistance, the mechanism is rarely reported. Here we generated two radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells ECA109 and Kyse150. We then found that Wnt signaling activity was higher in radioresistant cel...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0466-4

    authors: Zhao Y,Yi J,Tao L,Huang G,Chu X,Song H,Chen L

    更新日期:2018-04-01 00:00:00

  • Axotomy induces axonogenesis in hippocampal neurons through STAT3.

    abstract::After axotomy of embryonic hippocampal neurons in vitro, some of the axotomized axons lose their identity, and new axons arise and grow. This axotomy-induced axonogenesis requires importin, suggesting that some injury-induced signals are transported via axons to elicit axonogenesis after axotomy. In this study, we sho...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.59

    authors: Ohara R,Fujita Y,Hata K,Nakagawa M,Yamashita T

    更新日期:2011-06-23 00:00:00

  • Targeting the transcription factor receptor LXR to treat clear cell renal cell carcinoma: agonist or inverse agonist?

    abstract::Growing evidence indicates that clear cell renal cell carcinoma (ccRCC) is a metabolism-related disease. Changes in fatty acid (FA) and cholesterol metabolism play important roles in ccRCC development. As a nuclear transcription factor receptor, Liver X receptor (LXR) regulates a variety of key molecules associated wi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1654-6

    authors: Wu G,Wang Q,Xu Y,Li J,Zhang H,Qi G,Xia Q

    更新日期:2019-05-28 00:00:00

  • Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer.

    abstract::The high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were establishe...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1898-1

    authors: Herreros-Pomares A,de-Maya-Girones JD,Calabuig-Fariñas S,Lucas R,Martínez A,Pardo-Sánchez JM,Alonso S,Blasco A,Guijarro R,Martorell M,Escorihuela E,Chiara MD,Duréndez E,Gandía C,Forteza J,Sirera R,Jantus-Lewintre E,Farr

    更新日期:2019-09-10 00:00:00

  • GALNT6 promotes invasion and metastasis of human lung adenocarcinoma cells through O-glycosylating chaperone protein GRP78.

    abstract::Lung adenocarcinoma remains a threat to human health due to its high rate of recurrence and distant metastasis. However, the molecular mechanism underlying lung adenocarcinoma metastasis remains yet incompletely understood. Here, we show that upregulated expression of polypeptide N-acetylgalactosaminyltransferase6 (GA...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2537-6

    authors: Song J,Liu W,Wang J,Hao J,Wang Y,You X,Du X,Zhou Y,Ben J,Zhang X,Ye M,Wang Q

    更新日期:2020-05-11 00:00:00

  • JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry.

    abstract::Mitochondrial membrane potential provides a valuable indicator of cells' health and functional status. Cytometry- and microscopy-based analyses, in combination with fluorescent probes, are widely used to study mitochondrial behavior related to cellular pathways, most notably - apoptosis. The cyanine dye JC-1 (5,5',6,6...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.171

    authors: Perelman A,Wachtel C,Cohen M,Haupt S,Shapiro H,Tzur A

    更新日期:2012-11-22 00:00:00

  • FOXF2 acts as a crucial molecule in tumours and embryonic development.

    abstract::As a key member of the forkhead box transcription factors, forkhead box F2 (FOXF2) serves as a transcriptional regulator and regulates downstream gene expression in embryonic development, metabolism and in some common diseases, such as stroke and gastroparesis. Recent studies have shown that aberrant expression of FOX...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-020-2604-z

    authors: He W,Kang Y,Zhu W,Zhou B,Jiang X,Ren C,Guo W

    更新日期:2020-06-05 00:00:00

  • CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.

    abstract::It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CS...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.379

    authors: Ffrench B,Gasch C,Hokamp K,Spillane C,Blackshields G,Mahgoub TM,Bates M,Kehoe L,Mooney A,Doyle R,Doyle B,O'Donnell D,Gleeson N,Hennessy BT,Stordal B,O'Riain C,Lambkin H,O'Toole S,O'Leary JJ,Gallagher MF

    更新日期:2017-10-19 00:00:00

  • HLA-B-associated transcript 3 (Bat3/Scythe) negatively regulates Smad phosphorylation in BMP signaling.

    abstract::Members of the transforming growth factor-β (TGF-β) superfamily participate in numerous biological phenomena in multiple tissues, including in cell proliferation, differentiation, and migration. TGF-β superfamily proteins therefore have prominent roles in wound healing, fibrosis, bone formation, and carcinogenesis. Ho...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.114

    authors: Goto K,Tong KI,Ikura J,Okada H

    更新日期:2011-12-01 00:00:00

  • Cellular and molecular response of human macrophages exposed to Aggregatibacter actinomycetemcomitans leukotoxin.

    abstract::Aggregatibacter (Actinobacillus) actinomycetemcomitans is a facultative anaerobic gram-negative bacterium associated with severe forms of periodontitis. A leukotoxin, which belongs to the repeats-in-toxin family, is believed to be one of its virulence factors and to have an important role in the bacterium's pathogenic...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.6

    authors: Kelk P,Abd H,Claesson R,Sandström G,Sjöstedt A,Johansson A

    更新日期:2011-03-10 00:00:00

  • Hyperosmotic stress enhances cytotoxicity of SMAC mimetics.

    abstract::Inhibitors of apoptosis (IAP) proteins contribute to cell death resistance in malignancies and emerged as promising targets in cancer therapy. Currently, small molecules mimicking the IAP-antagonizing activity of endogenous second mitochondria-derived activator of caspases (SMAC) are evaluated in phase 1/2 clinical tr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.355

    authors: Bittner S,Knoll G,Ehrenschwender M

    更新日期:2017-08-03 00:00:00

  • Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment.

    abstract::Glucocorticoids (GCs) are metabolic hormones with immunosuppressive effects that have proven effective drugs against childhood acute lymphoblastic leukemia (ALL). Yet, the role of metabolic reprogramming in GC-induced ALL cell death is poorly understood. GCs efficiently block glucose uptake and metabolism in ALL cells...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0625-7

    authors: Dyczynski M,Vesterlund M,Björklund AC,Zachariadis V,Janssen J,Gallart-Ayala H,Daskalaki E,Wheelock CE,Lehtiö J,Grandér D,Tamm KP,Nilsson R

    更新日期:2018-08-28 00:00:00

  • The role of m6A modification in physiology and disease.

    abstract::Similar to DNA epigenetic modifications, multiple reversible chemical modifications on RNAs have been uncovered in a new layer of epigenetic modification. N6-methyladenosine (m6A), a modification that occurs in ~30% transcripts, is dynamically regulated by writer complex (methylase) and eraser (RNA demethylase) protei...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-020-03143-z

    authors: Yang C,Hu Y,Zhou B,Bao Y,Li Z,Gong C,Yang H,Wang S,Xiao Y

    更新日期:2020-11-08 00:00:00

  • EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury.

    abstract::We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and dist...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.262

    authors: Tsenkina Y,Ricard J,Runko E,Quiala-Acosta MM,Mier J,Liebl DJ

    更新日期:2015-10-15 00:00:00

  • Tryptophan-kynurenine pathway attenuates β-catenin-dependent pro-parasitic role of STING-TICAM2-IRF3-IDO1 signalosome in Toxoplasma gondii infection.

    abstract::Recent studies have documented the diverse role of host immunity in infection by the protozoan parasite, Toxoplasma gondii. However, the contribution of the β-catenin pathway in this process has not been explored. Here, we show that AKT-mediated phosphorylated β-catenin supports T. gondii multiplication which is arres...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1420-9

    authors: Majumdar T,Sharma S,Kumar M,Hussain MA,Chauhan N,Kalia I,Sahu AK,Rana VS,Bharti R,Haldar AK,Singh AP,Mazumder S

    更新日期:2019-02-15 00:00:00

  • Adrenomedullin alleviates the pyroptosis of Leydig cells by promoting autophagy via the ROS-AMPK-mTOR axis.

    abstract::Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells expose...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1728-5

    authors: Li MY,Zhu XL,Zhao BX,Shi L,Wang W,Hu W,Qin SL,Chen BH,Zhou PH,Qiu B,Gao Y,Liu BL

    更新日期:2019-06-20 00:00:00

  • The long non-coding RNA SNHG1 promotes glioma progression by competitively binding to miR-194 to regulate PHLDA1 expression.

    abstract::Long non-coding RNAs (lncRNAs) play a vital role in tumourigenesis, including that of glioma. Small nucleolar RNA host gene 1 (SNHG1) is a relatively novel lncRNA that is involved in the development of multiple human tumours. However, its underlying molecular mechanism in glioma has not been completely clarified. In t...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1698-7

    authors: Liu L,Shi Y,Shi J,Wang H,Sheng Y,Jiang Q,Chen H,Li X,Dong J

    更新日期:2019-06-12 00:00:00

  • Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy.

    abstract::Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02860-9

    authors: Masson C,García-García D,Bitard J,Grellier ÉK,Roger JE,Perron M

    更新日期:2020-08-14 00:00:00

  • A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis.

    abstract::Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspa...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.219

    authors: Kim JH,Lee DK,Kim J,Choi S,Park W,Ha KS,Kim TH,Choe J,Won MH,Kwon YG,Kim YM

    更新日期:2017-05-18 00:00:00