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 |
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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 |
doi_str_mv | 10.3892/etm.2021.10481 |
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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<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<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<0.05). Noggin and BMPs significantly decreased ratios of p-p38/p38, compared with those of the DNCP group (P<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<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<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<0.05). Noggin and BMPs significantly decreased ratios of p-p38/p38, compared with those of the DNCP group (P<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<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<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<0.05). Noggin and BMPs significantly decreased ratios of p-p38/p38, compared with those of the DNCP group (P<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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