The miR‐193a‐3p‐MAP3k3 Signaling Axis Regulates Substrate Topography‐Induced Osteogenesis of Bone Marrow Stem Cells
Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular si...
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| Veröffentlicht in: | Advanced science 2020-01, Vol.7 (1), p.1901412-n/a, Article 1901412 |
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| creator | Lv, Yan Huang, Ying Xu, Mingming Heng, Boon Chin Yang, Congchong Cao, Cen Hu, Zhewen Liu, Wenwen Chi, Xiaopei Gao, Min Zhang, Xuehui Wei, Yan Deng, Xuliang |
| description | Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue‐induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature‐induced osteogenic differentiation group is different from that of the chemical‐factors‐induced osteogenic differentiation group. miR‐193a‐3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis−inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway—the mitogen‐activated protein kinase (MAPK) pathway. Loss‐ and gain‐of‐function experiments demonstrate that miR‐193a‐3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic‐lineage‐related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies.
Topographical feature‐induced bone marrow stem cells (BMSCs) lineage specification is different from that of chemical‐factors‐induced BMSCs lineage specification in terms of microRNA expression. MiR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic differentiation of BMSCs. As an outlook, when designing implantable biomedical devices or orthopedic substitutes, more attention should be focused on their biophysical properties. |
| doi_str_mv | 10.1002/advs.201901412 |
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Topographical feature‐induced bone marrow stem cells (BMSCs) lineage specification is different from that of chemical‐factors‐induced BMSCs lineage specification in terms of microRNA expression. MiR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic differentiation of BMSCs. As an outlook, when designing implantable biomedical devices or orthopedic substitutes, more attention should be focused on their biophysical properties.</description><identifier>ISSN: 2198-3844</identifier><identifier>EISSN: 2198-3844</identifier><identifier>DOI: 10.1002/advs.201901412</identifier><identifier>PMID: 31921551</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Biomedical materials ; biophysical cues induced‐osteogenic differentiation ; Bone marrow ; Chemistry ; Chemistry, Multidisciplinary ; Defects ; Gene expression ; Investigations ; Materials Science ; Materials Science, Multidisciplinary ; MicroRNAs ; miR‐193a‐3p‐MAP3k3 signaling axis ; Morphology ; Nanoscience & Nanotechnology ; Physical Sciences ; Principal components analysis ; Protein expression ; Proteins ; Scanning electron microscopy ; Science & Technology ; Science & Technology - Other Topics ; Stem cells ; Technology ; topographical cues ; Topography ; Variance analysis</subject><ispartof>Advanced science, 2020-01, Vol.7 (1), p.1901412-n/a, Article 1901412</ispartof><rights>2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>25</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000496027400001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c5299-a4fac0416cd20736b8eec24c9095a3bfa47b91dc6468599bb729f48b43fbead33</citedby><cites>FETCH-LOGICAL-c5299-a4fac0416cd20736b8eec24c9095a3bfa47b91dc6468599bb729f48b43fbead33</cites><orcidid>0000-0003-1838-6274</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947707/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947707/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1418,2103,2115,11567,27929,27930,28253,45579,45580,46057,46481,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31921551$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lv, Yan</creatorcontrib><creatorcontrib>Huang, Ying</creatorcontrib><creatorcontrib>Xu, Mingming</creatorcontrib><creatorcontrib>Heng, Boon Chin</creatorcontrib><creatorcontrib>Yang, Congchong</creatorcontrib><creatorcontrib>Cao, Cen</creatorcontrib><creatorcontrib>Hu, Zhewen</creatorcontrib><creatorcontrib>Liu, Wenwen</creatorcontrib><creatorcontrib>Chi, Xiaopei</creatorcontrib><creatorcontrib>Gao, Min</creatorcontrib><creatorcontrib>Zhang, Xuehui</creatorcontrib><creatorcontrib>Wei, Yan</creatorcontrib><creatorcontrib>Deng, Xuliang</creatorcontrib><title>The miR‐193a‐3p‐MAP3k3 Signaling Axis Regulates Substrate Topography‐Induced Osteogenesis of Bone Marrow Stem Cells</title><title>Advanced science</title><addtitle>ADV SCI</addtitle><addtitle>Adv Sci (Weinh)</addtitle><description>Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue‐induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature‐induced osteogenic differentiation group is different from that of the chemical‐factors‐induced osteogenic differentiation group. miR‐193a‐3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis−inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway—the mitogen‐activated protein kinase (MAPK) pathway. Loss‐ and gain‐of‐function experiments demonstrate that miR‐193a‐3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic‐lineage‐related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies.
Topographical feature‐induced bone marrow stem cells (BMSCs) lineage specification is different from that of chemical‐factors‐induced BMSCs lineage specification in terms of microRNA expression. MiR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic differentiation of BMSCs. As an outlook, when designing implantable biomedical devices or orthopedic substitutes, more attention should be focused on their biophysical properties.</description><subject>Biomedical materials</subject><subject>biophysical cues induced‐osteogenic differentiation</subject><subject>Bone marrow</subject><subject>Chemistry</subject><subject>Chemistry, Multidisciplinary</subject><subject>Defects</subject><subject>Gene expression</subject><subject>Investigations</subject><subject>Materials Science</subject><subject>Materials Science, Multidisciplinary</subject><subject>MicroRNAs</subject><subject>miR‐193a‐3p‐MAP3k3 signaling axis</subject><subject>Morphology</subject><subject>Nanoscience & Nanotechnology</subject><subject>Physical Sciences</subject><subject>Principal components analysis</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Scanning electron microscopy</subject><subject>Science & Technology</subject><subject>Science & Technology - Other Topics</subject><subject>Stem cells</subject><subject>Technology</subject><subject>topographical cues</subject><subject>Topography</subject><subject>Variance analysis</subject><issn>2198-3844</issn><issn>2198-3844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>AOWDO</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqNks1uEzEUhUcIRKvQLUs0EhsklOCfO57xBikNf5FaFTWBreXx3Jm6TMbBnmmp2PAIPCNPgtOEqGUDG_vK_s7Rte9JkqeUTCgh7JWursKEESoJBcoeJIeMymLMC4CHd-qD5CiES0IIzXgOtHicHHAqGc0yeph8X15gurLnv378pJLruPF1XE6nH_kXni5s0-nWdk06_WZDeo7N0OoeQ7oYytD7WKZLt3aN1-uLmyibd9VgsErPQo-uwQ5DVLk6PXYdpqfae3edLnpcpTNs2_AkeVTrNuDRbh8ln969Xc4-jE_O3s9n05OxyZiUYw21NgSoMBUjORdlgWgYGElkpnlZa8hLSSsjQBSZlGWZM1lDUQKvS9QV56NkvvWtnL5Ua29X2t8op626PXC-Udr31rSogEkgTJQgsAadGVkbUlcVyxijmAuMXq-3XuuhXGFlsIvf0N4zvX_T2QvVuCslJOR5bH-UvNgZePd1wNCrlQ0mfofu0A1BMc4Fg4LHYY2S53-hl27wcSC3FFAuRMEiNdlSxrsQPNb7ZihRm5ioTUzUPiZR8OzuE_b4n1BEoNgC11i6OhiLncE9FoMEUhCWA9lkamZ73VvXzdzQ9VH68v-lkYYdbVu8-Uffavrm84ICSP4bxL_tDw</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Lv, Yan</creator><creator>Huang, Ying</creator><creator>Xu, Mingming</creator><creator>Heng, Boon Chin</creator><creator>Yang, Congchong</creator><creator>Cao, Cen</creator><creator>Hu, Zhewen</creator><creator>Liu, Wenwen</creator><creator>Chi, Xiaopei</creator><creator>Gao, Min</creator><creator>Zhang, Xuehui</creator><creator>Wei, Yan</creator><creator>Deng, Xuliang</creator><general>Wiley</general><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1838-6274</orcidid></search><sort><creationdate>20200101</creationdate><title>The miR‐193a‐3p‐MAP3k3 Signaling Axis Regulates Substrate Topography‐Induced Osteogenesis of Bone Marrow Stem Cells</title><author>Lv, Yan ; Huang, Ying ; Xu, Mingming ; Heng, Boon Chin ; Yang, Congchong ; Cao, Cen ; Hu, Zhewen ; Liu, Wenwen ; Chi, Xiaopei ; Gao, Min ; Zhang, Xuehui ; Wei, Yan ; Deng, Xuliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5299-a4fac0416cd20736b8eec24c9095a3bfa47b91dc6468599bb729f48b43fbead33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomedical materials</topic><topic>biophysical cues induced‐osteogenic differentiation</topic><topic>Bone marrow</topic><topic>Chemistry</topic><topic>Chemistry, Multidisciplinary</topic><topic>Defects</topic><topic>Gene expression</topic><topic>Investigations</topic><topic>Materials Science</topic><topic>Materials Science, Multidisciplinary</topic><topic>MicroRNAs</topic><topic>miR‐193a‐3p‐MAP3k3 signaling axis</topic><topic>Morphology</topic><topic>Nanoscience & Nanotechnology</topic><topic>Physical Sciences</topic><topic>Principal components analysis</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Scanning electron microscopy</topic><topic>Science & Technology</topic><topic>Science & Technology - Other Topics</topic><topic>Stem cells</topic><topic>Technology</topic><topic>topographical cues</topic><topic>Topography</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lv, Yan</creatorcontrib><creatorcontrib>Huang, Ying</creatorcontrib><creatorcontrib>Xu, Mingming</creatorcontrib><creatorcontrib>Heng, Boon Chin</creatorcontrib><creatorcontrib>Yang, Congchong</creatorcontrib><creatorcontrib>Cao, Cen</creatorcontrib><creatorcontrib>Hu, Zhewen</creatorcontrib><creatorcontrib>Liu, Wenwen</creatorcontrib><creatorcontrib>Chi, Xiaopei</creatorcontrib><creatorcontrib>Gao, Min</creatorcontrib><creatorcontrib>Zhang, Xuehui</creatorcontrib><creatorcontrib>Wei, Yan</creatorcontrib><creatorcontrib>Deng, Xuliang</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Advanced science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lv, Yan</au><au>Huang, Ying</au><au>Xu, Mingming</au><au>Heng, Boon Chin</au><au>Yang, Congchong</au><au>Cao, Cen</au><au>Hu, Zhewen</au><au>Liu, Wenwen</au><au>Chi, Xiaopei</au><au>Gao, Min</au><au>Zhang, Xuehui</au><au>Wei, Yan</au><au>Deng, Xuliang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The miR‐193a‐3p‐MAP3k3 Signaling Axis Regulates Substrate Topography‐Induced Osteogenesis of Bone Marrow Stem Cells</atitle><jtitle>Advanced science</jtitle><stitle>ADV SCI</stitle><addtitle>Adv Sci (Weinh)</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>7</volume><issue>1</issue><spage>1901412</spage><epage>n/a</epage><pages>1901412-n/a</pages><artnum>1901412</artnum><issn>2198-3844</issn><eissn>2198-3844</eissn><abstract>Substrate topographical features induce osteogenic differentiation of bone marrow stem cells (BMSCs), but the underlying mechanisms are unclear. As microRNAs (miRNAs) play key roles in osteogenesis and bone regeneration, it would be meaningful to elucidate the roles of miRNAs in the intracellular signaling cascade of topographical cue‐induced osteogenic differentiation. In this study, the miRNA expression profile of the topographical feature‐induced osteogenic differentiation group is different from that of the chemical‐factors‐induced osteogenic differentiation group. miR‐193a‐3p is sensitive to substrate topographical features and its downregulation enhances osteogenic differentiation only in the absence of osteogenesis−inducing medium. Also, substrate topographical features specifically activate a nonclassical osteogenetic pathway—the mitogen‐activated protein kinase (MAPK) pathway. Loss‐ and gain‐of‐function experiments demonstrate that miR‐193a‐3p regulates the MAPK pathway by targeting the MAP3k3 gene. In conclusion, this data indicates that different osteogenic‐lineage‐related intracellular signaling cascades are triggered in BMSCs subjected to biophysical or chemical stimulation. Moreover, the miR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic lineage specification of BMSCs, and hence may be a promising molecular target for bone regenerative therapies.
Topographical feature‐induced bone marrow stem cells (BMSCs) lineage specification is different from that of chemical‐factors‐induced BMSCs lineage specification in terms of microRNA expression. MiR‐193a‐3p‐MAP3k3 signaling axis plays a pivotal role in the transduction of biophysical cues from the substrate to regulate the osteogenic differentiation of BMSCs. As an outlook, when designing implantable biomedical devices or orthopedic substitutes, more attention should be focused on their biophysical properties.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>31921551</pmid><doi>10.1002/advs.201901412</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-1838-6274</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biomedical materials biophysical cues induced‐osteogenic differentiation Bone marrow Chemistry Chemistry, Multidisciplinary Defects Gene expression Investigations Materials Science Materials Science, Multidisciplinary MicroRNAs miR‐193a‐3p‐MAP3k3 signaling axis Morphology Nanoscience & Nanotechnology Physical Sciences Principal components analysis Protein expression Proteins Scanning electron microscopy Science & Technology Science & Technology - Other Topics Stem cells Technology topographical cues Topography Variance analysis |
| title | The miR‐193a‐3p‐MAP3k3 Signaling Axis Regulates Substrate Topography‐Induced Osteogenesis of Bone Marrow Stem Cells |
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