Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation
SCAPs (Stem Cells from Apical Papilla), derived from the apex of forming wisdom teeth, extracted from teenagers for orthodontic reasons, belong to the MSCs (Mesenchymal Stromal Cells) family. They have multipotent differentiation capabilities and are a potentially powerful model for investigating st...
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2025-01-01
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| author | Damien Le Nihouannen Claudine Boiziau Sylvie Rey Nicole Agadzhanian Nathalie Dusserre Fabrice Cordelières Muriel Priault Helene Boeuf |
| author_facet | Damien Le Nihouannen Claudine Boiziau Sylvie Rey Nicole Agadzhanian Nathalie Dusserre Fabrice Cordelières Muriel Priault Helene Boeuf |
| author_sort | Damien Le Nihouannen |
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| description | SCAPs (Stem Cells from Apical Papilla), derived from the apex of forming wisdom teeth, extracted from teenagers for orthodontic reasons, belong to the MSCs (Mesenchymal Stromal Cells) family. They have multipotent differentiation capabilities and are a potentially powerful model for investigating strategies of clinical cell therapies. Since autophagy—a regulated self-eating process—was proposed to be essential in osteogenesis, we investigated its involvement in the SCAP model. By using a combination of chemical and genetic approaches to inhibit autophagy, we studied early and late events of osteoblastic differentiation. We showed that blocking the formation of autophagosomes with verteporfin did not induce a dramatic alteration in early osteoblastic differentiation monitored by ALP (alkaline phosphatase) activity. However, blocking the autophagy flux with bafilomycin A1 led to ALP repression. Strikingly, the mineralization process was observed with both compounds, with calcium phosphate (CaP) nodules that remained inside cells under bafilomycin A1 treatment and numerous but smaller CaP nodules after verteporfin treatment. In contrast, deletion of <i>Atg5</i> or <i>Atg7</i>, two genes involved in the formation of autophagosomes and essential to trigger canonical autophagy, indicated that both genes could be involved differently in the mineralization process with a modification of the ALP activity while final mineralization was not altered. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-4a25ce32f76d44a09a82cef3deb0f92d2025-01-24T13:26:50ZengMDPI AGCells2073-44092025-01-0114214610.3390/cells14020146Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell AdaptationDamien Le Nihouannen0Claudine Boiziau1Sylvie Rey2Nicole Agadzhanian3Nathalie Dusserre4Fabrice Cordelières5Muriel Priault6Helene Boeuf7The Laboratory for the Bioengineering of Tissues (BioTis U1026), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceThe Laboratory for the Bioengineering of Tissues (BioTis U1026), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceThe Laboratory for the Bioengineering of Tissues (BioTis U1026), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceThe Laboratory for the Bioengineering of Tissues (BioTis U1026), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceThe Laboratory for the Bioengineering of Tissues (BioTis U1026), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceBordeaux Imaging Center (BIC), US4, UAR 3420, National Center for Scientific Research (CNRS), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceNational Center for Scientific Research (CNRS), Institut de Biochimie et Génétique Cellulaires (IBGC), UMR 5095, Université de Bordeaux, F-33000 Bordeaux, FranceThe Laboratory for the Bioengineering of Tissues (BioTis U1026), National Institute of Health and Medical Research (INSERM), Université de Bordeaux, F-33000 Bordeaux, FranceSCAPs (Stem Cells from Apical Papilla), derived from the apex of forming wisdom teeth, extracted from teenagers for orthodontic reasons, belong to the MSCs (Mesenchymal Stromal Cells) family. They have multipotent differentiation capabilities and are a potentially powerful model for investigating strategies of clinical cell therapies. Since autophagy—a regulated self-eating process—was proposed to be essential in osteogenesis, we investigated its involvement in the SCAP model. By using a combination of chemical and genetic approaches to inhibit autophagy, we studied early and late events of osteoblastic differentiation. We showed that blocking the formation of autophagosomes with verteporfin did not induce a dramatic alteration in early osteoblastic differentiation monitored by ALP (alkaline phosphatase) activity. However, blocking the autophagy flux with bafilomycin A1 led to ALP repression. Strikingly, the mineralization process was observed with both compounds, with calcium phosphate (CaP) nodules that remained inside cells under bafilomycin A1 treatment and numerous but smaller CaP nodules after verteporfin treatment. In contrast, deletion of <i>Atg5</i> or <i>Atg7</i>, two genes involved in the formation of autophagosomes and essential to trigger canonical autophagy, indicated that both genes could be involved differently in the mineralization process with a modification of the ALP activity while final mineralization was not altered.https://www.mdpi.com/2073-4409/14/2/146mesenchymal stem cellsSCAPscanonical autophagyalternative autophagybafilomycin A1verteporfin |
| spellingShingle | Damien Le Nihouannen Claudine Boiziau Sylvie Rey Nicole Agadzhanian Nathalie Dusserre Fabrice Cordelières Muriel Priault Helene Boeuf Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation Cells mesenchymal stem cells SCAPs canonical autophagy alternative autophagy bafilomycin A1 verteporfin |
| title | Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation |
| title_full | Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation |
| title_fullStr | Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation |
| title_full_unstemmed | Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation |
| title_short | Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation |
| title_sort | inhibiting autophagy by chemicals during scaps osteodifferentiation elicits disorganized mineralization while the knock out of i atg5 7 i genes leads to cell adaptation |
| topic | mesenchymal stem cells SCAPs canonical autophagy alternative autophagy bafilomycin A1 verteporfin |
| url | https://www.mdpi.com/2073-4409/14/2/146 |
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