DNCP induces the differentiation of induced pluripotent stem cells into odontoblasts by activating the Smad/p‑Smad and p38/p‑p38 signaling pathways

In recent years, stem cells have been studied for treating tooth loss. The present study aimed to investigate the roles of dentin non-collagen protein (DNCP)-associated microenvironments in the differentiation of induced pluripotent stem cells (iPSCs) into dentin cells. iPSCs were cultured and ident...

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Veröffentlicht in:Experimental and therapeutic medicine 2021-12, Vol.22 (6), Article 1361
Hauptverfasser: Liu, Zhe, Zhan, Aiping, Fan, Sumeng, Liao, Lan, Lian, Wenwei
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creator Liu, Zhe
Zhan, Aiping
Fan, Sumeng
Liao, Lan
Lian, Wenwei
description In recent years, stem cells have been studied for treating tooth loss. The present study aimed to investigate the roles of dentin non-collagen protein (DNCP)-associated microenvironments in the differentiation of induced pluripotent stem cells (iPSCs) into dentin cells. iPSCs were cultured and identified by examining octamer-binding transcription-factor-4 (Oct-4) and sex-determining region-Y-2 (Sox-2) expression. iPSCs were differentiated by culturing DNCP-associated microenvironments (containing specific growth factors), and they were divided into control, DNCP, DNCP+bone morphogenetic proteins (BMPs) and DNCP+Noggin (a BMP inhibitor) groups. Msh homeobox 1 (Msx-1), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1) mRNA expression was evaluated using reverse transcription-quantitative PCR. The levels of p38, phosphorylated (p)-p38, Smad and p-Smad were determined by western blotting. Upon treatment with mouse embryonic fibroblasts, iPSCs-dependent embryoid bodies (EBs) were successfully generated. iPSCs exhibited increased Oct-4 and Sox-2 expression. Differentiated iPSCs had higher expression levels of DSPP, DMP-1 and Msx-1 in the DNCP group compared with those in the control group (P
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The present study aimed to investigate the roles of dentin non-collagen protein (DNCP)-associated microenvironments in the differentiation of induced pluripotent stem cells (iPSCs) into dentin cells. iPSCs were cultured and identified by examining octamer-binding transcription-factor-4 (Oct-4) and sex-determining region-Y-2 (Sox-2) expression. iPSCs were differentiated by culturing DNCP-associated microenvironments (containing specific growth factors), and they were divided into control, DNCP, DNCP+bone morphogenetic proteins (BMPs) and DNCP+Noggin (a BMP inhibitor) groups. Msh homeobox 1 (Msx-1), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1) mRNA expression was evaluated using reverse transcription-quantitative PCR. The levels of p38, phosphorylated (p)-p38, Smad and p-Smad were determined by western blotting. Upon treatment with mouse embryonic fibroblasts, iPSCs-dependent embryoid bodies (EBs) were successfully generated. iPSCs exhibited increased Oct-4 and Sox-2 expression. Differentiated iPSCs had higher expression levels of DSPP, DMP-1 and Msx-1 in the DNCP group compared with those in the control group (P&lt;0.05). Noggin treatment significantly downregulated, while BMPs administration significantly increased the expression levels of DSPP, DMP-1 and Msx-1 compared with those of the DNCP group (P&lt;0.05). The ratios of p-p38/p38 and p-Smad/Smad were significantly higher in the DNCP group compared with those in the control group (P&lt;0.05). Noggin and BMPs significantly decreased ratios of p-p38/p38, compared with those of the DNCP group (P&lt;0.05). In conclusion, DNCP induced the differentiation of iPSCs into odontoblasts by activating the Smad/p-Smad and p38/p-p38 signaling pathways. Key words: dentin non-collagen protein, induced pluripotent stem cells, bone morphogenetic proteins, differentiation, odontoblasts</description><identifier>ISSN: 1792-0981</identifier><identifier>EISSN: 1792-1015</identifier><identifier>DOI: 10.3892/etm.2021.10481</identifier><identifier>PMID: 34659507</identifier><language>eng</language><publisher>Spandidos Publications</publisher><subject>Analysis ; Bone morphogenetic proteins ; Care and treatment ; Composition ; Dentin ; Diagnosis ; Identification and classification ; Messenger RNA ; Observations ; Odontogenesis ; Risk factors ; Tooth loss</subject><ispartof>Experimental and therapeutic medicine, 2021-12, Vol.22 (6), Article 1361</ispartof><rights>COPYRIGHT 2021 Spandidos Publications</rights><rights>Copyright © 2020, Spandidos Publications 2020</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c319t-4ca8d49804c81ed7b9203994dbf758c005ed0e3c6887871f7b8e805c494585643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515507/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515507/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Liu, Zhe</creatorcontrib><creatorcontrib>Zhan, Aiping</creatorcontrib><creatorcontrib>Fan, Sumeng</creatorcontrib><creatorcontrib>Liao, Lan</creatorcontrib><creatorcontrib>Lian, Wenwei</creatorcontrib><title>DNCP induces the differentiation of induced pluripotent stem cells into odontoblasts by activating the Smad/p‑Smad and p38/p‑p38 signaling pathways</title><title>Experimental and therapeutic medicine</title><description>In recent years, stem cells have been studied for treating tooth loss. The present study aimed to investigate the roles of dentin non-collagen protein (DNCP)-associated microenvironments in the differentiation of induced pluripotent stem cells (iPSCs) into dentin cells. iPSCs were cultured and identified by examining octamer-binding transcription-factor-4 (Oct-4) and sex-determining region-Y-2 (Sox-2) expression. iPSCs were differentiated by culturing DNCP-associated microenvironments (containing specific growth factors), and they were divided into control, DNCP, DNCP+bone morphogenetic proteins (BMPs) and DNCP+Noggin (a BMP inhibitor) groups. Msh homeobox 1 (Msx-1), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1) mRNA expression was evaluated using reverse transcription-quantitative PCR. The levels of p38, phosphorylated (p)-p38, Smad and p-Smad were determined by western blotting. Upon treatment with mouse embryonic fibroblasts, iPSCs-dependent embryoid bodies (EBs) were successfully generated. iPSCs exhibited increased Oct-4 and Sox-2 expression. Differentiated iPSCs had higher expression levels of DSPP, DMP-1 and Msx-1 in the DNCP group compared with those in the control group (P&lt;0.05). Noggin treatment significantly downregulated, while BMPs administration significantly increased the expression levels of DSPP, DMP-1 and Msx-1 compared with those of the DNCP group (P&lt;0.05). The ratios of p-p38/p38 and p-Smad/Smad were significantly higher in the DNCP group compared with those in the control group (P&lt;0.05). Noggin and BMPs significantly decreased ratios of p-p38/p38, compared with those of the DNCP group (P&lt;0.05). In conclusion, DNCP induced the differentiation of iPSCs into odontoblasts by activating the Smad/p-Smad and p38/p-p38 signaling pathways. Key words: dentin non-collagen protein, induced pluripotent stem cells, bone morphogenetic proteins, differentiation, odontoblasts</description><subject>Analysis</subject><subject>Bone morphogenetic proteins</subject><subject>Care and treatment</subject><subject>Composition</subject><subject>Dentin</subject><subject>Diagnosis</subject><subject>Identification and classification</subject><subject>Messenger RNA</subject><subject>Observations</subject><subject>Odontogenesis</subject><subject>Risk factors</subject><subject>Tooth loss</subject><issn>1792-0981</issn><issn>1792-1015</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNptUctqGzEUFaEhCUm2XQu6tiONpBlpUwjuE0JbaLsWGj1slRlpGMkJ3vUXusr_5Ut67ZhCIdLiXO45OtLVQeg1JUsmVXPj67hsSEOXlHBJT9AF7VSzoISKV8eaKEnP0XUpvwgs0VIpxRk6Z7wVSpDuAj2--7L6hmNyW-sLrhuPXQzBzz7VaGrMCedwpB2ehu0cp1yBxKX6EVs_DAXomnF2GaAfTKkF9ztsbI334JDWB9fvo3E309PvP_sCmwRmTB4agLjEdTLDXjuZunkwu3KFToMZir8-4iX6-eH9j9Wnxd3Xj59Xt3cLy6iqC26NdFxJwq2k3nW9aghTirs-dEJaGNk74pltpexkR0PXSy-JsFxxIUXL2SV6--w7bfvROwujzWbQ0xxHM-90NlH_z6S40et8r6WgAn4QDN48G6zN4HVMIYPMjrFYfQu3toI2goFq-YIKtvNjtDn5EKH_0gE751JmH_49iRK9D19D-Hofvj6Ez_4Cu_WkVQ</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Liu, Zhe</creator><creator>Zhan, Aiping</creator><creator>Fan, Sumeng</creator><creator>Liao, Lan</creator><creator>Lian, Wenwei</creator><general>Spandidos Publications</general><general>D.A. Spandidos</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20211201</creationdate><title>DNCP induces the differentiation of induced pluripotent stem cells into odontoblasts by activating the Smad/p‑Smad and p38/p‑p38 signaling pathways</title><author>Liu, Zhe ; Zhan, Aiping ; Fan, Sumeng ; Liao, Lan ; Lian, Wenwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-4ca8d49804c81ed7b9203994dbf758c005ed0e3c6887871f7b8e805c494585643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Bone morphogenetic proteins</topic><topic>Care and treatment</topic><topic>Composition</topic><topic>Dentin</topic><topic>Diagnosis</topic><topic>Identification and classification</topic><topic>Messenger RNA</topic><topic>Observations</topic><topic>Odontogenesis</topic><topic>Risk factors</topic><topic>Tooth loss</topic><toplevel>online_resources</toplevel><creatorcontrib>Liu, Zhe</creatorcontrib><creatorcontrib>Zhan, Aiping</creatorcontrib><creatorcontrib>Fan, Sumeng</creatorcontrib><creatorcontrib>Liao, Lan</creatorcontrib><creatorcontrib>Lian, Wenwei</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental and therapeutic medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Zhe</au><au>Zhan, Aiping</au><au>Fan, Sumeng</au><au>Liao, Lan</au><au>Lian, Wenwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNCP induces the differentiation of induced pluripotent stem cells into odontoblasts by activating the Smad/p‑Smad and p38/p‑p38 signaling pathways</atitle><jtitle>Experimental and therapeutic medicine</jtitle><date>2021-12-01</date><risdate>2021</risdate><volume>22</volume><issue>6</issue><artnum>1361</artnum><issn>1792-0981</issn><eissn>1792-1015</eissn><abstract>In recent years, stem cells have been studied for treating tooth loss. The present study aimed to investigate the roles of dentin non-collagen protein (DNCP)-associated microenvironments in the differentiation of induced pluripotent stem cells (iPSCs) into dentin cells. iPSCs were cultured and identified by examining octamer-binding transcription-factor-4 (Oct-4) and sex-determining region-Y-2 (Sox-2) expression. iPSCs were differentiated by culturing DNCP-associated microenvironments (containing specific growth factors), and they were divided into control, DNCP, DNCP+bone morphogenetic proteins (BMPs) and DNCP+Noggin (a BMP inhibitor) groups. Msh homeobox 1 (Msx-1), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1) mRNA expression was evaluated using reverse transcription-quantitative PCR. The levels of p38, phosphorylated (p)-p38, Smad and p-Smad were determined by western blotting. Upon treatment with mouse embryonic fibroblasts, iPSCs-dependent embryoid bodies (EBs) were successfully generated. iPSCs exhibited increased Oct-4 and Sox-2 expression. Differentiated iPSCs had higher expression levels of DSPP, DMP-1 and Msx-1 in the DNCP group compared with those in the control group (P&lt;0.05). Noggin treatment significantly downregulated, while BMPs administration significantly increased the expression levels of DSPP, DMP-1 and Msx-1 compared with those of the DNCP group (P&lt;0.05). The ratios of p-p38/p38 and p-Smad/Smad were significantly higher in the DNCP group compared with those in the control group (P&lt;0.05). Noggin and BMPs significantly decreased ratios of p-p38/p38, compared with those of the DNCP group (P&lt;0.05). In conclusion, DNCP induced the differentiation of iPSCs into odontoblasts by activating the Smad/p-Smad and p38/p-p38 signaling pathways. Key words: dentin non-collagen protein, induced pluripotent stem cells, bone morphogenetic proteins, differentiation, odontoblasts</abstract><pub>Spandidos Publications</pub><pmid>34659507</pmid><doi>10.3892/etm.2021.10481</doi><oa>free_for_read</oa></addata></record>
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subjects Analysis
Bone morphogenetic proteins
Care and treatment
Composition
Dentin
Diagnosis
Identification and classification
Messenger RNA
Observations
Odontogenesis
Risk factors
Tooth loss
title DNCP induces the differentiation of induced pluripotent stem cells into odontoblasts by activating the Smad/p‑Smad and p38/p‑p38 signaling pathways
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