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10.1089/scd.2020.0061 http://scihub22266oqcxt.onion/10.1089/scd.2020.0061 32799744!ä!32799744 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 282.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 282.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 282.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 282.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 282.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 282.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Stem+Cells+Dev 2020 ; 29 (20): 1309-1319 Nephropedia Template TP {{tp|p=32799744|t=2020. Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis in the Degenerative Disc Microenvironment Through Activation of the HIF-1alpha/YAP Signaling Pathway |pdf=|usr=}}{{32799744}} gab.com Text Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis in the Degenerative Disc Microenvironment Through Activation of the HIF-1alpha/YAP Signaling Pathway JO: Stem Cells Dev http://www.kidney.de/pget.php?&tw=1&pmid=32799744 #FOAvip Stem cell therapy provides an attractive solution for intervertebral disc (IVD) degeneration. However, the degenerative microenvironment, characterized by excessive mechanical loading and hypoxia, remains an obstacle for the long-lasting survival of exogenous transplanted stem cells. Whether and how bone marrow mesenchymal stem cells (BMSCs) adapt to the hostile microenvironment remain unclear. In this study, CoCl(2) and mechanical compression were simultaneously used to simulate the hypoxic and overloaded microenvironment of IVDs in vitro. Compression had a proapoptotic effect through activation of the mitochondrial apoptotic pathway, while hypoxia exerted a prosurvival effect counteracting compression-induced apoptosis. Inhibiting the transcriptional activity of hypoxia inducible factor 1 subunit alpha (HIF-1alpha) by chetomin reversed the antiapoptotic effect of hypoxia. Furthermore, HIF-1alpha promoted dephosphorylation and activation of yes-associated protein (YAP) in hypoxic conditions. Conversely, both YAP inhibition and increased cell apoptosis were observed after inhibition through chetomin or YAP inhibitor verteporfin. Immunofluorescence staining and coimmunoprecipitation assays revealed that YAP could interact directly with HIF-1alpha and colocalize in the nucleus. Taken together, our results demonstrated that hypoxia protected BMSCs against compression-induced apoptosis in the degenerative disc microenvironment through activation of the HIF-1alpha/YAP signaling pathway. Thus, regulation of HIF-1alpha/YAP signaling might provide novel insights for promoting long-lasting BMSC survival and optimizing stem cell therapy for IVD degeneration. Twit Text FOAVip Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis in the Degenerative Disc Microenvironment Through Activation of the HIF-1alpha/YAP Signaling Pathway ????Stem Cells Dev http://www.kidney.de/pget.php?&tw=1&pmid=32799744 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32799744 #FOAvip English Wikipedia <ref>{{Cite pmid|32799744}}</ref> Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis in the Degenerative Disc Microenvironment Through Activation of the HIF-1alpha/YAP Signaling Pathway #MMPMID32799744 Wang Z; Cui M; Qu Y; He R; Wu W; Lin H; Shao Z Stem Cells Dev 2020[Oct]; 29 (20): 1309-1319 PMID32799744show ga Stem cell therapy provides an attractive solution for intervertebral disc (IVD) degeneration. However, the degenerative microenvironment, characterized by excessive mechanical loading and hypoxia, remains an obstacle for the long-lasting survival of exogenous transplanted stem cells. Whether and how bone marrow mesenchymal stem cells (BMSCs) adapt to the hostile microenvironment remain unclear. In this study, CoCl(2) and mechanical compression were simultaneously used to simulate the hypoxic and overloaded microenvironment of IVDs in vitro. Compression had a proapoptotic effect through activation of the mitochondrial apoptotic pathway, while hypoxia exerted a prosurvival effect counteracting compression-induced apoptosis. Inhibiting the transcriptional activity of hypoxia inducible factor 1 subunit alpha (HIF-1alpha) by chetomin reversed the antiapoptotic effect of hypoxia. Furthermore, HIF-1alpha promoted dephosphorylation and activation of yes-associated protein (YAP) in hypoxic conditions. Conversely, both YAP inhibition and increased cell apoptosis were observed after inhibition through chetomin or YAP inhibitor verteporfin. Immunofluorescence staining and coimmunoprecipitation assays revealed that YAP could interact directly with HIF-1alpha and colocalize in the nucleus. Taken together, our results demonstrated that hypoxia protected BMSCs against compression-induced apoptosis in the degenerative disc microenvironment through activation of the HIF-1alpha/YAP signaling pathway. Thus, regulation of HIF-1alpha/YAP signaling might provide novel insights for promoting long-lasting BMSC survival and optimizing stem cell therapy for IVD degeneration. |*Apoptosis[MESH] |*Cellular Microenvironment/drug effects[MESH] |*Cytoprotection/drug effects[MESH] |*Signal Transduction/drug effects[MESH] |*Stress, Mechanical[MESH] |Animals[MESH] |Cell Hypoxia/drug effects[MESH] |Cell Survival/drug effects[MESH] |Cobalt/pharmacology[MESH] |Female[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism[MESH] |Intervertebral Disc Degeneration/*pathology[MESH] |Intracellular Signaling Peptides and Proteins/*metabolism[MESH] |Mesenchymal Stem Cells/*cytology/drug effects[MESH] |Models, Biological[MESH] |Rats, Sprague-Dawley[MESH]Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compr(epmc).pdf DeepDyve Pubget Overpricing