Enhanced osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis: a study based on a three-dimensional biomimetic environment.

Abstract:

:The mechanism of pathological osteogenesis in Ankylosing spondylitis (AS) is largely unknown. Our previous studies demonstrated that the imbalance between BMP-2 and Noggin secretion induces abnormal osteogenic differentiation of marrow-derived mesenchymal stem cells (MSCs) from AS patients in a two-dimensional culture environment. In this study, HA/β-TCP scaffolds were further used as a three-dimensional (3D) biomimetic culture system to mimic the bone microenvironment in vivo to determine the abnormal osteogenic differentiation of AS-MSCs. We demonstrated that when cultured in HA/β-TCP scaffolds, AS-MSCs had a stronger osteogenic differentiation capacity than that of MSCs from healthy donors (HD-MSCs) in vitro and in vivo. This dysfunction resulted from BMP2 overexpression in AS-MSCs, which excessively activated the Smad1/5/8 and ERK signalling pathways and finally led to enhanced osteogenic differentiation. Both the signalling pathway inhibitors and siRNAs inhibiting BMP2 expression could rectify the enhanced osteogenic differentiation of AS-MSCs. Furthermore, BMP2 expression in ossifying entheses was significantly higher in AS patients. In summary, our study demonstrated that AS-MSCs possess enhanced osteogenic differentiation in HA/β-TCP scaffolds as a 3D biomimetic microenvironment because of BMP2 overexpression, but not Noggin. These results provide insights into the mechanism of pathological osteogenesis, which can aid in the development of niche-targeting medications for AS.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Zheng G,Xie Z,Wang P,Li J,Li M,Cen S,Tang S,Liu W,Ye G,Li Y,Wang S,Wu X,Su H,Wu Y,Shen H

doi

10.1038/s41419-019-1586-1

subject

Has Abstract

pub_date

2019-04-25 00:00:00

pages

350

issue

5

issn

2041-4889

pii

10.1038/s41419-019-1586-1

journal_volume

10

pub_type

杂志文章
  • Histone deacetylase 6 inhibition rescues axonal transport impairments and prevents the neurotoxicity of HIV-1 envelope protein gp120.

    abstract::Despite successful antiretroviral drug therapy, a subset of human immunodeficiency virus-1 (HIV)-positive individuals still display synaptodendritic simplifications and functional cognitive impairments referred to as HIV-associated neurocognitive disorders (HANDs). The neurological damage observed in HAND subjects can...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1920-7

    authors: Wenzel ED,Speidell A,Flowers SA,Wu C,Avdoshina V,Mocchetti I

    更新日期:2019-09-12 00:00:00

  • Inflammation and Notch signaling: a crosstalk with opposite effects on tumorigenesis.

    abstract::The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1-4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, D...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2016.408

    authors: Fazio C,Ricciardiello L

    更新日期:2016-12-08 00:00:00

  • Salt-inducible kinase 1 regulates bone anabolism via the CRTC1-CREB-Id1 axis.

    abstract::New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary pr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1915-4

    authors: Kim MK,Kwon JO,Song MK,Kim B,Kim H,Lee ZH,Koo SH,Kim HH

    更新日期:2019-10-31 00:00:00

  • Survival or death: disequilibrating the oncogenic and tumor suppressive autophagy in cancer.

    abstract::Autophagy (macroautophagy) is an evolutionarily conserved lysosomal degradation process, in which a cell degrades long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed the core molecular machinery of autophagy in carcinogenesis; however, the intricate relationship between autophagy a...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2013.422

    authors: Liu B,Wen X,Cheng Y

    更新日期:2013-10-31 00:00:00

  • Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis.

    abstract::In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.361

    authors: Ruiz A,Rockfield S,Taran N,Haller E,Engelman RW,Flores I,Panina-Bordignon P,Nanjundan M

    更新日期:2016-01-14 00:00:00

  • Correction: CXCR2 expression on granulocyte and macrophage progenitors under tumor conditions contributes to mo-MDSC generation via SAP18/ERK/STAT3.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-1869-6

    authors: Han X,Shi H,Sun Y,Shang C,Luan T,Wang D,Ba X,Zeng X

    更新日期:2019-09-05 00:00:00

  • Consequences of blunting the mevalonate pathway in cancer identified by a pluri-omics approach.

    abstract::We have previously shown that the combination of statins and taxanes was a powerful trigger of HGT-1 human gastric cancer cells' apoptosis1. Importantly, several genes involved in the "Central carbon metabolism pathway in cancer", as reported in the Kyoto Encyclopedia of Genes and Genomes, were either up- (ACLY, ERBB2...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0761-0

    authors: Goulitquer S,Croyal M,Lalande J,Royer AL,Guitton Y,Arzur D,Durand S,Le Jossic-Corcos C,Bouchereau A,Potin P,Akoka S,Antignac JP,Krempf M,Ferchaud-Roucher V,Giraudeau P,Corcos L

    更新日期:2018-07-03 00:00:00

  • iASPP-PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation.

    abstract::Cytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0561-6

    authors: Gao K,Zhang Y,Shi Q,Zhang J,Zhang L,Sun H,Jiao D,Zhao X,Tao H,Wei Y,Wang Y,Saiyin H,Zhao SM,Li Y,Zhang P,Wang C

    更新日期:2018-05-01 00:00:00

  • Cancer cell-derived immunoglobulin G activates platelets by binding to platelet FcγRIIa.

    abstract::Tumor-associated thrombosis is the second leading risk factor for cancer patient death, and platelets activity is abnormal in cancer patients. Discovering the mechanism of platelet activation and providing effective targets for therapy are urgently needed. Cancer cell- derived IgG has been reported to regulate develop...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1367-x

    authors: Miao S,Shu D,Zhu Y,Lu M,Zhang Q,Pei Y,He AD,Ma R,Zhang B,Ming ZY

    更新日期:2019-01-28 00:00:00

  • Manipulating the air-filled zebrafish swim bladder as a neutrophilic inflammation model for acute lung injury.

    abstract::Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening diseases that are associated with high mortality rates due to treatment limitations. Neutrophils play key roles in the pathogenesis of ALI/ARDS by promoting the inflammation and injury of the alveolar mic...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.365

    authors: Zhang Y,Liu H,Yao J,Huang Y,Qin S,Sun Z,Xu Y,Wan S,Cheng H,Li C,Zhang X,Ke Y

    更新日期:2016-11-10 00:00:00

  • Extracellular ATP drives systemic inflammation, tissue damage and mortality.

    abstract::Systemic inflammatory response syndromes (SIRS) may be caused by both infectious and sterile insults, such as trauma, ischemia-reperfusion or burns. They are characterized by early excessive inflammatory cytokine production and the endogenous release of several toxic and damaging molecules. These are necessary to figh...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.70

    authors: Cauwels A,Rogge E,Vandendriessche B,Shiva S,Brouckaert P

    更新日期:2014-03-06 00:00:00

  • Cryo-thermal therapy induces macrophage polarization for durable anti-tumor immunity.

    abstract::Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1459-7

    authors: He K,Jia S,Lou Y,Liu P,Xu LX

    更新日期:2019-03-04 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

  • Gamma-ray irradiation promotes premature meiosis of spontaneously differentiating testis-ova in the testis of p53-deficient medaka (Oryzias latipes).

    abstract::In this study, the roles of p53 in impaired spermatogenic male germ cells of p53-deficient medaka were investigated by analyzing histological changes, and gene expressions of 42Sp50, Oct 4 and vitellogenin (VTG2) by RT-PCR or in situ hybridization in the testes. We found that a small number of oocyte-like cells (testi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.133

    authors: Yasuda T,Oda S,Li Z,Kimori Y,Kamei Y,Ishikawa T,Todo T,Mitani H

    更新日期:2012-10-04 00:00:00

  • Plumbagin inhibits the proliferation and survival of esophageal cancer cells by blocking STAT3-PLK1-AKT signaling.

    abstract::Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it requires novel treatment approaches and effective drugs. In the present study, we found that treatment with plumbagin, a natural compound, reduced proliferation and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0068-6

    authors: Cao YY,Yu J,Liu TT,Yang KX,Yang LY,Chen Q,Shi F,Hao JJ,Cai Y,Wang MR,Lu WH,Zhang Y

    更新日期:2018-01-16 00:00:00

  • Sirt3 suppresses calcium oxalate-induced renal tubular epithelial cell injury via modification of FoxO3a-mediated autophagy.

    abstract::High oxalic acid and calcium oxalate (CaOx)-induced renal tubular epithelial cell (TEC) injury plays a key role in nephrolithiasis. However, the mechanism remains unknown. Gene array analysis of the mice nephrolithiasis model indicated significant downregulation of sirtuin 3 (Sirt3) and activation of mitogen-activated...

    journal_title:Cell death & disease

    pub_type: 杂志文章,收录出版

    doi:10.1038/s41419-018-1169-6

    authors: Peng Y,Yang C,Shi X,Li L,Dong H,Liu C,Fang Z,Wang Z,Ming S,Liu M,Xie B,Gao X,Sun Y

    更新日期:2019-01-15 00:00:00

  • Parkin regulates NF-κB by mediating site-specific ubiquitination of RIPK1.

    abstract::Parkin (Park2), a RING-between-RING-type E3 ubiquitin ligase, has been implicated in regulating NF-κB. Mutations in Parkin are associated with Parkinson's disease. Here we investigated the interaction of Parkin with Receptor-interacting protein kinase 1 (RIPK1) kinase, a key mediator of multiple signaling pathways act...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0770-z

    authors: Wang Y,Shan B,Liang Y,Wei H,Yuan J

    更新日期:2018-06-28 00:00:00

  • The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage.

    abstract::Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite t...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.381

    authors: Yoo SJ,Cho B,Lee D,Son G,Lee YB,Soo Han H,Kim E,Moon C,Moon C

    更新日期:2017-08-17 00:00:00

  • Regulatory roles of miR-22/Redd1-mediated mitochondrial ROS and cellular autophagy in ionizing radiation-induced BMSC injury.

    abstract::Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/R...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1373-z

    authors: Liu Z,Li T,Zhu F,Deng S,Li X,He Y

    更新日期:2019-03-07 00:00:00

  • Cystathionine β-synthase (CBS) deficiency suppresses erythropoiesis by disrupting expression of heme biosynthetic enzymes and transporter.

    abstract::The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS-/-) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, inclu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1951-0

    authors: Zhao P,Qian C,Chen YJ,Sheng Y,Ke Y,Qian ZM

    更新日期:2019-09-24 00:00:00

  • ERα-mediated alterations in circ_0023642 and miR-490-5p signaling suppress bladder cancer invasion.

    abstract::Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we ex...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1827-3

    authors: Wu L,Zhang M,Qi L,Zu X,Li Y,Liu L,Chen M,Li Y,He W,Hu X,Mo M,Ou Z,Wang L

    更新日期:2019-08-27 00:00:00

  • B7-H3 regulates KIF15-activated ERK1/2 pathway and contributes to radioresistance in colorectal cancer.

    abstract::As an important modality for the local control of colorectal cancer (CRC), radiotherapy or neoadjuvant radiotherapy is widely applied in the clinic, but radioresistance has become a major obstacle for CRC radiotherapy. Here we reported that B7-H3, an important costimulatory molecule, is associated with radioresistance...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03041-4

    authors: Ma Y,Zhan S,Lu H,Wang R,Xu Y,Zhang G,Cao L,Shi T,Zhang X,Chen W

    更新日期:2020-10-03 00:00:00

  • Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway.

    abstract::Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.282

    authors: Moon HG,Cao Y,Yang J,Lee JH,Choi HS,Jin Y

    更新日期:2015-12-10 00:00:00

  • microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.

    abstract::The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target o...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0131-3

    authors: Zhang Y,Wei Y,Li X,Liang X,Wang L,Song J,Zhang X,Zhang C,Niu J,Zhang P,Ren Z,Tang B

    更新日期:2018-01-26 00:00:00

  • The interaction of interleukin-8 and PTEN inactivation promotes the malignant progression of head and neck squamous cell carcinoma via the STAT3 pathway.

    abstract::Interleukin-8 (IL-8) expression correlates with poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism is poorly understood. In this study, we found that overexpression of IL-8 correlated with poor outcome in HNSCC patients. IL-8 significantly increased ce...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2627-5

    authors: Xu Q,Ma H,Chang H,Feng Z,Zhang C,Yang X

    更新日期:2020-05-29 00:00:00

  • Correction: C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis.

    abstract::The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-018-0834-0

    authors: Jiang Q,Wang F,Shi L,Zhao X,Gong M,Liu W,Song C,Li Q,Chen Y,Wu H,Han D

    更新日期:2018-07-16 00:00:00

  • A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.

    abstract::Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.437

    authors: Di Angelantonio S,Murana E,Cocco S,Scala F,Bertollini C,Molinari MG,Lauro C,Bregestovski P,Limatola C,Ragozzino D

    更新日期:2014-10-30 00:00:00

  • Proton irradiation orchestrates macrophage reprogramming through NFκB signaling.

    abstract::Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0757-9

    authors: Genard G,Wera AC,Huart C,Le Calve B,Penninckx S,Fattaccioli A,Tabarrant T,Demazy C,Ninane N,Heuskin AC,Lucas S,Michiels C

    更新日期:2018-06-27 00:00:00

  • Wnt3a disrupts GR-TEAD4-PPARγ2 positive circuits and cytoskeletal rearrangement in a β-catenin-dependent manner during early adipogenesis.

    abstract::Adipogenesis is a process which induces or represses many genes in a way to drive irreversible changes of cell phenotypes; lipid accumulation, round cell-shape, secreting many adipokines. As a master transcription factor (TF), PPARγ2 induces several target genes to orchestrate these adipogenic changes. Thus induction ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1249-7

    authors: Park B,Chang S,Lee GJ,Kang B,Kim JK,Park H

    更新日期:2019-01-08 00:00:00

  • Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans.

    abstract::Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berber...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1706-y

    authors: Wu L,Xia M,Duan Y,Zhang L,Jiang H,Hu X,Yan H,Zhang Y,Gu Y,Shi H,Li J,Gao X,Li J

    更新日期:2019-06-13 00:00:00