European journal of cell biology最新文献

{"title":"Mitf, with Yki and STRIPAK-PP2A, is a key determinant of form and fate in the progenitor epithelium of the Drosophila eye.","authors":"Tianyi Zhang ,&nbsp;Qingxiang Zhou ,&nbsp;Nisveta Jusić ,&nbsp;Wenwen Lu ,&nbsp;Francesca Pignoni ,&nbsp;Scott J. Neal","doi":"10.1016/j.ejcb.2024.151421","DOIUrl":"10.1016/j.ejcb.2024.151421","url":null,"abstract":"<div><p>The Microphthalmia-associated Transcription Factor (MITF) governs numerous cellular and developmental processes. In mice, it promotes specification and differentiation of the retinal pigmented epithelium (RPE), and in humans, some mutations in MITF induce congenital eye malformations. Herein, we explore the function and regulation of Mitf in <em>Drosophila</em> eye development and uncover two roles. We find that knockdown of <em>Mitf</em> results in retinal displacement (RDis), a phenotype associated with abnormal eye formation. Mitf functions in the peripodial epithelium (PE), a retinal support tissue akin to the RPE, to suppress RDis, via the Hippo pathway effector Yorkie (Yki). Yki physically interacts with Mitf and can modify its transcriptional activity <em>in vitro</em>. Severe loss of Mitf, instead, results in the de-repression of retinogenesis in the PE, precluding its development. This activity of Mitf requires the protein phosphatase 2 A holoenzyme STRIPAK-PP2A, but not Yki; Mitf transcriptional activity is potentiated by STRIPAK-PP2A <em>in vitro</em> and <em>in vivo</em>. Knockdown of STRIPAK-PP2A results in cytoplasmic retention of Mitf <em>in vivo</em> and in its decreased stability <em>in vitro</em>, highlighting two potential mechanisms for the control of Mitf function by STRIPAK-PP2A. Thus, Mitf functions in a context-dependent manner as a key determinant of form and fate in the <em>Drosophila</em> eye progenitor epithelium.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151421"},"PeriodicalIF":6.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000384/pdfft?md5=4a8d8c5178cb796eea36268acf8caf2c&pid=1-s2.0-S0171933524000384-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141056221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear receptor Nur77 regulates immunomechanics of macrophages","authors":"Sanne C. Lith ,&nbsp;Tom M.J. Evers ,&nbsp;Beatriz Marton Freire ,&nbsp;Claudia M. van Tie ,&nbsp;Winnie. G. Vosa ,&nbsp;Alireza Mashaghi ,&nbsp;Carlie J.M. de Vries","doi":"10.1016/j.ejcb.2024.151419","DOIUrl":"10.1016/j.ejcb.2024.151419","url":null,"abstract":"<div><p>Nuclear receptor Nur77 plays a pivotal role in immune regulation across various tissues, influencing pro-inflammatory signaling pathways and cellular metabolism. While cellular mechanics have been implicated in inflammation, the contribution of Nur77 to these mechanical processes remains elusive. Macrophages exhibit remarkable plasticity in their morphology and mechanics, enabling them to adapt and execute essential inflammatory functions, such as navigating through inflamed tissue and pathogen engulfment. However, the precise regulatory mechanisms governing these dynamic changes in macrophage mechanics during inflammation remain poorly understood. To establish the potential correlation of Nur77 with cellular mechanics, we compared bone marrow-derived macrophages (BMDMs) from wild-type (WT) and Nur77-deficient (Nur77-KO) mice and employed cytoskeletal imaging, single-cell acoustic force spectroscopy (AFS), migration and phagocytosis assays, and RNA-sequencing. Our findings reveal that Nur77-KO BMDMs exhibit changes to their actin networks compared to WT BMDMs, which is associated with a stiffer and more rigid phenotype. Subsequent <em>in vitro</em> experiments validated our observations, showcasing that Nur77 deficiency leads to enhanced migration, reduced adhesion, and increased phagocytic activity. The transcriptomics data confirmed altered mechanics-related pathways in Nur77-deficient macrophage that are accompanied by a robust pro-inflammatory phenotype. Utilizing previously obtained ChIP-data, we revealed that Nur77 directly targets differentially expressed genes associated with cellular mechanics. In conclusion, while Nur77 is recognized for its role in reducing inflammation of macrophages by inhibiting the expression of pro-inflammatory genes, our study identifies a novel regulatory mechanism where Nur77 governs macrophage inflammation through the modulation of expression of genes involved in cellular mechanics. Our findings suggest that immune regulation by Nur77 may be partially mediated through alterations in cellular mechanics, highlighting a potential avenue for therapeutic targeting.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151419"},"PeriodicalIF":6.6,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000360/pdfft?md5=575b7283c26b62adf52a1d283c8b48d0&pid=1-s2.0-S0171933524000360-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141046522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanoresponsive ETS1 causes endothelial dysfunction and arterialization in varicose veins via NOTCH4/DLL4 signaling","authors":"B.J. Sreelakshmi ,&nbsp;C.L. Karthika ,&nbsp;S. Ahalya ,&nbsp;S.R. Kalpana ,&nbsp;C.C. Kartha ,&nbsp;S. Sumi","doi":"10.1016/j.ejcb.2024.151420","DOIUrl":"10.1016/j.ejcb.2024.151420","url":null,"abstract":"<div><p>Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. <em>In vitro</em> microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151420"},"PeriodicalIF":6.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000372/pdfft?md5=930f260a21d087265164bb72c353f8c9&pid=1-s2.0-S0171933524000372-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders","authors":"Takeshi Kondo ,&nbsp;Yuka Okada ,&nbsp;Saika Shizuya ,&nbsp;Naoko Yamaguchi ,&nbsp;Shigetsugu Hatakeyama ,&nbsp;Kenta Maruyama","doi":"10.1016/j.ejcb.2024.151418","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151418","url":null,"abstract":"<div><p>The nervous and immune systems are highly developed, and each performs specialized physiological functions. However, they work together, and their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, and more general metabolites, are essential for the appropriate regulation of both systems. Tryptophan, an essential amino acid, is converted into functional molecules such as serotonin and kynurenine, both of which play important roles in the nervous and immune systems. The role of kynurenine metabolites in neurodegenerative and psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity of the kynurenine pathway is a critical risk factor for septic shock. In this review, we first outline neuroimmune interactions and tryptophan derivatives and then summarized the changes in tryptophan metabolism in neurological disorders. Finally, we discuss the potential of tryptophan derivatives as therapeutic targets for neuroimmune disorders.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151418"},"PeriodicalIF":6.6,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000359/pdfft?md5=6598740727395858da1ff92f8a07ccbe&pid=1-s2.0-S0171933524000359-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140901336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanotransduction in stem cells","authors":"Carmelo Ferrai ,&nbsp;Carsten Schulte","doi":"10.1016/j.ejcb.2024.151417","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151417","url":null,"abstract":"<div><p>Nowadays, it is an established concept that the capability to reach a specialised cell identity via differentiation, as in the case of multi- and pluripotent stem cells, is not only determined by biochemical factors, but that also physical aspects of the microenvironment play a key role; interpreted by the cell through a force-based signalling pathway called mechanotransduction. However, the intricate ties between the elements involved in mechanotransduction, such as the extracellular matrix, the glycocalyx, the cell membrane, Integrin adhesion complexes, Cadherin-mediated cell/cell adhesion, the cytoskeleton, and the nucleus, are still far from being understood in detail. Here we report what is currently known about these elements in general and their specific interplay in the context of multi- and pluripotent stem cells. We furthermore merge this overview to a more comprehensive picture, that aims to cover the whole mechanotransductive pathway from the cell/microenvironment interface to the regulation of the chromatin structure in the nucleus. Ultimately, with this review we outline the current picture of the interplay between mechanotransductive cues and epigenetic regulation and how these processes might contribute to stem cell dynamics and fate.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151417"},"PeriodicalIF":6.6,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000347/pdfft?md5=118e0595f2c13c31e0810c2c1c4f1b74&pid=1-s2.0-S0171933524000347-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140901337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the 3-mercaptopyruvate sulfurtransferase in colon/colorectal cancers","authors":"Katarina Matyasova ,&nbsp;Andrea Soltysova ,&nbsp;Petr Babula ,&nbsp;Olga Krizanova ,&nbsp;Veronika Liskova","doi":"10.1016/j.ejcb.2024.151415","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151415","url":null,"abstract":"<div><p>The 3-mercaptopyruvate sulfurtransferase (MPST) is a protein persulfidase, occurring mainly in mitochondria. Although function of this protein in cancer cells has been already studied, no clear outcome can be postulated up to now. Therefore, we focused on the determination of function of MPST in colon (HCT116 cells)/colorectal (DLD1 cells) cancers. <em>In silico</em> analysis revealed that in gastrointestinal cancers, MPST together with its binding partners can be either of a high risk or might have a protective effect. Silencing of <em>MPST</em> gene resulted in decreased ATP, while acetyl-CoA levels were elevated. Increased apoptosis was detected in cells with silenced <em>MPST</em> gene, which was accompanied by decrease in mitochondrial membrane potential, but no changes in IP₃ receptor’s protein. Mitochondria underwent activation of fission and elevated DRP1 expression after <em>MPST</em> silencing. Proliferation and migration of DLD1 and HCT116 cells were markedly affected, showing the importance of MPST protein in colon/colorectal cancer development.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151415"},"PeriodicalIF":6.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000323/pdfft?md5=40bcbadcf22b02eeb742c65d27b13fae&pid=1-s2.0-S0171933524000323-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Septin-dependent defense mechanisms against Pseudomonas aeruginosa are stalled in cystic fibrosis bronchial epithelial cells","authors":"Sylvain Brax ,&nbsp;Clémence Gaudin ,&nbsp;Claire Calmel ,&nbsp;Pierre-Yves Boëlle ,&nbsp;Harriet Corvol ,&nbsp;Manon Ruffin ,&nbsp;Loïc Guillot","doi":"10.1016/j.ejcb.2024.151416","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151416","url":null,"abstract":"<div><p>Airway epithelial cells form a physical barrier against inhaled pathogens and coordinate innate immune responses in the lungs. Bronchial cells in people with cystic fibrosis (pwCF) are colonized by <em>Pseudomonas aeruginosa</em> because of the accumulation of mucus in the lower airways and an altered immune response. This leads to chronic inflammation, lung tissue damage, and accelerated decline in lung function. Thus, identifying the molecular factors involved in the host response in the airways is crucial for developing new therapeutic strategies. The septin (SEPT) cytoskeleton is involved in tissue barrier integrity and anti-infective responses. SEPT7 is critical for maintaining SEPT complexes and for sensing pathogenic microbes. In the lungs, SEPT7 may be involved in the epithelial barrier resistance to infection; however, its role in cystic fibrosis (CF) <em>P. aeruginosa</em> infection is unknown. This study aimed to investigate the role of SEPT7 in controlling <em>P. aeruginosa</em> infection in bronchial epithelial cells, particularly in CF. The study findings showed that SEPT7 encages <em>P. aeruginosa</em> in bronchial epithelial cells and its inhibition downregulates the expression of other SEPTs. In addition, <em>P. aeruginosa</em> does not regulate SEPT7 expression. Finally, we found that inhibiting SEPT7 expression in bronchial epithelial cells (BEAS-2B 16HBE14o- and primary cells) resulted in higher levels of internalized <em>P. aeruginosa</em> and decreased IL-6 production during infection, suggesting a crucial role of SEPT7 in the host response against this bacterium. However, these effects were not observed in the CF cells (16HBE14o-/F508del and primary cells) which may explain the persistence of infection in pwCF. The study findings suggest the modification of SEPT7 expression as a potential approach for the anti-infective control of <em>P. aeruginosa</em>, particularly in CF.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151416"},"PeriodicalIF":6.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000335/pdfft?md5=ca8af7ea625def8665005329ab10adb1&pid=1-s2.0-S0171933524000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140605208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of NRAS Q61K with a ligand-induced pocket near switch II","authors":"Teklab Gebregiworgis ,&nbsp;Jonathan Yui-Lai Chan ,&nbsp;Douglas A. Kuntz ,&nbsp;Gilbert G. Privé ,&nbsp;Christopher B. Marshall ,&nbsp;Mitsuhiko Ikura","doi":"10.1016/j.ejcb.2024.151414","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151414","url":null,"abstract":"<div><p>The RAS isoforms (KRAS, HRAS and NRAS) have distinct cancer type-specific profiles. NRAS mutations are the second most prevalent RAS mutations in skin and hematological malignancies. Although RAS proteins were considered undruggable for decades, isoform and mutation-specific investigations have produced successful RAS inhibitors that are either specific to certain mutants, isoforms (pan-KRAS) or target all RAS proteins (pan-RAS). While extensive structural and biochemical investigations have focused mainly on K- and H-RAS mutations, NRAS mutations have received less attention, and the most prevalent NRAS mutations in human cancers, Q61K and Q61R, are rare in K- and H-RAS. This manuscript presents a crystal structure of the NRAS Q61K mutant in the GTP-bound form. Our structure reveals a previously unseen pocket near switch II induced by the binding of a ligand to the active form of the protein. This observation reveals a binding site that can potentially be exploited for development of inhibitors against mutant NRAS. Furthermore, the well-resolved catalytic site of this GTPase bound to native GTP provides insight into the stalled GTP hydrolysis observed for NRAS-Q61K.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151414"},"PeriodicalIF":6.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000311/pdfft?md5=ff3510fc9ce1ff5ba8e4b90d8544a6d3&pid=1-s2.0-S0171933524000311-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmembrane signaling through single-spanning receptors modulated by phase separation at the cell surface","authors":"Toshiyuki Murai","doi":"10.1016/j.ejcb.2024.151413","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151413","url":null,"abstract":"<div><p>A wide variety of transmembrane signals are transduced by cell-surface receptors that activate intracellular signaling molecules. In particular, receptor clustering in the plasma membrane plays a critical role in these processes. Single-spanning or single-pass transmembrane proteins are among the most significant types of membrane receptors, which include adhesion receptors, such as integrins, CD44, cadherins, and receptor tyrosine kinases. Elucidating the molecular mechanisms underlying the regulation of the activity of these receptors is of great significance. Liquid–liquid phase separation (LLPS) is a recently emerging paradigm in cellular physiology for the ubiquitous regulation of the spatiotemporal dynamics of various signaling pathways. This study describes the emerging features of transmembrane signaling through single-spanning receptors from the perspective of phase separation. Possible physicochemical modulations of LLPS-based transmembrane signaling are also discussed.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151413"},"PeriodicalIF":6.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017193352400030X/pdfft?md5=f355123dc16d3a979343eb4f372eaca9&pid=1-s2.0-S017193352400030X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis","authors":"Sven Schmidt ,&nbsp;Felicia A.M. Klampfleuthner ,&nbsp;Tobias Renkawitz ,&nbsp;Solvig Diederichs","doi":"10.1016/j.ejcb.2024.151412","DOIUrl":"https://doi.org/10.1016/j.ejcb.2024.151412","url":null,"abstract":"<div><p>Mesenchymal stromal cells (MSCs) that are promising for cartilage tissue engineering secrete high amounts of prostaglandin E2 (PGE2), an immunoactive mediator involved in endochondral bone development. This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect makes PGE2 not only a promising option for future combinatorial approaches to direct MSC tissue engineering approaches into chondral instead of endochondral development but could potentially have implications for the use of COX-2-selective inhibitors in osteoarthritis pain management.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 2","pages":"Article 151412"},"PeriodicalIF":6.6,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000293/pdfft?md5=8b143b5af9017e9a4c35bc7b9f4396f2&pid=1-s2.0-S0171933524000293-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}