AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells
We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor...
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| Veröffentlicht in: | Cell biochemistry and biophysics 2015-04, Vol.71 (3), p.1543-1551 |
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| creator | Qu, Zhiguo Guo, Shengnan Fang, Guojun Cui, Zhenghong Liu, Ying |
| description | We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8 weeks post fracture for analysis. The fracture line became less defined at 4 weeks and disappeared at 8 weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50 % compared to the hUC-MSCs with plasma group and decreased 70 % compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs. |
| doi_str_mv | 10.1007/s12013-014-0378-6 |
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To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8 weeks post fracture for analysis. The fracture line became less defined at 4 weeks and disappeared at 8 weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50 % compared to the hUC-MSCs with plasma group and decreased 70 % compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs.</description><identifier>ISSN: 1085-9195</identifier><identifier>EISSN: 1559-0283</identifier><identifier>DOI: 10.1007/s12013-014-0378-6</identifier><identifier>PMID: 25413962</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Anesthesia ; Animals ; Biochemistry ; Biological and Medical Physics ; Biomechanical Phenomena - drug effects ; Biomedical and Life Sciences ; Biophysics ; Biotechnology ; Bone Regeneration - drug effects ; Cell Adhesion ; Cell Biology ; Cell Differentiation ; Enzyme Inhibitors - pharmacology ; Gene Expression Regulation, Enzymologic - drug effects ; Humans ; Life Sciences ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - cytology ; Original Paper ; Osteogenesis - drug effects ; Pharmacology/Toxicology ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Stem cells ; Tibial Fractures - pathology ; Tibial Fractures - physiopathology ; Tibial Fractures - surgery ; Umbilical Cord - cytology</subject><ispartof>Cell biochemistry and biophysics, 2015-04, Vol.71 (3), p.1543-1551</ispartof><rights>The Author(s) 2014</rights><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-71b086b9a3d07af98981ad7a7b156679e51d111d6ce974f2f7ee8c114c7ce6f03</citedby><cites>FETCH-LOGICAL-c573t-71b086b9a3d07af98981ad7a7b156679e51d111d6ce974f2f7ee8c114c7ce6f03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12013-014-0378-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12013-014-0378-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25413962$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qu, Zhiguo</creatorcontrib><creatorcontrib>Guo, Shengnan</creatorcontrib><creatorcontrib>Fang, Guojun</creatorcontrib><creatorcontrib>Cui, Zhenghong</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><title>AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells</title><title>Cell biochemistry and biophysics</title><addtitle>Cell Biochem Biophys</addtitle><addtitle>Cell Biochem Biophys</addtitle><description>We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8 weeks post fracture for analysis. The fracture line became less defined at 4 weeks and disappeared at 8 weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50 % compared to the hUC-MSCs with plasma group and decreased 70 % compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs.</description><subject>Anesthesia</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomechanical Phenomena - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Biotechnology</subject><subject>Bone Regeneration - drug effects</subject><subject>Cell Adhesion</subject><subject>Cell Biology</subject><subject>Cell Differentiation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Original Paper</subject><subject>Osteogenesis - drug effects</subject><subject>Pharmacology/Toxicology</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Stem cells</subject><subject>Tibial Fractures - pathology</subject><subject>Tibial Fractures - physiopathology</subject><subject>Tibial Fractures - surgery</subject><subject>Umbilical Cord - cytology</subject><issn>1085-9195</issn><issn>1559-0283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUtv1DAUhSMEoqXwA9igSGzYBHz99gZpOjxFeQima8txbmZSJU6xk1bz73E0pSpISKx8pfP5-FyfongK5CUQol4loARYRYBXhCldyXvFMQhhKkI1u59nokVlwIij4lFKF4RQSjh_WBxRwYEZSY-LfvVpU35z0-7a7ctV26KfUnk6Biy_4xYDRjd1Yyi7UH4ZwxyWeRPRTdiU1920K8-Huus77_pyPcameoOxu8raZ0wY_G4_ZOHHhEO5xr5Pj4sHresTPrk5T4rzd2836w_V2df3H9ers8oLxaZKQU20rI1jDVGuNdpocI1yqgYhpTIooAGARno0ire0VYjaA3CvPMqWsJPi9cH3cq4HbDyGKbreXsZucHFvR9fZP5XQ7ex2vLKcc8OkzAYvbgzi-HPGNNmhSz6v4AKOc7KgNDNAGRH_gxJBOScmo8__Qi_GOYb8Exak5pILLZfwcKB8HFOK2N7mBmKX2u2hdptrt0vtdsn77O7Ctzd-95wBegBSlsIW452n_-n6C1-muAE</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Qu, Zhiguo</creator><creator>Guo, Shengnan</creator><creator>Fang, Guojun</creator><creator>Cui, Zhenghong</creator><creator>Liu, Ying</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150401</creationdate><title>AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells</title><author>Qu, Zhiguo ; Guo, Shengnan ; Fang, Guojun ; Cui, Zhenghong ; Liu, Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-71b086b9a3d07af98981ad7a7b156679e51d111d6ce974f2f7ee8c114c7ce6f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anesthesia</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and Medical Physics</topic><topic>Biomechanical Phenomena - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biophysics</topic><topic>Biotechnology</topic><topic>Bone Regeneration - drug effects</topic><topic>Cell Adhesion</topic><topic>Cell Biology</topic><topic>Cell Differentiation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Original Paper</topic><topic>Osteogenesis - drug effects</topic><topic>Pharmacology/Toxicology</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Stem cells</topic><topic>Tibial Fractures - pathology</topic><topic>Tibial Fractures - physiopathology</topic><topic>Tibial Fractures - surgery</topic><topic>Umbilical Cord - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qu, Zhiguo</creatorcontrib><creatorcontrib>Guo, Shengnan</creatorcontrib><creatorcontrib>Fang, Guojun</creatorcontrib><creatorcontrib>Cui, Zhenghong</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qu, Zhiguo</au><au>Guo, Shengnan</au><au>Fang, Guojun</au><au>Cui, Zhenghong</au><au>Liu, Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells</atitle><jtitle>Cell biochemistry and biophysics</jtitle><stitle>Cell Biochem Biophys</stitle><addtitle>Cell Biochem Biophys</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>71</volume><issue>3</issue><spage>1543</spage><epage>1551</epage><pages>1543-1551</pages><issn>1085-9195</issn><eissn>1559-0283</eissn><abstract>We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8 weeks post fracture for analysis. The fracture line became less defined at 4 weeks and disappeared at 8 weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50 % compared to the hUC-MSCs with plasma group and decreased 70 % compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>25413962</pmid><doi>10.1007/s12013-014-0378-6</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anesthesia Animals Biochemistry Biological and Medical Physics Biomechanical Phenomena - drug effects Biomedical and Life Sciences Biophysics Biotechnology Bone Regeneration - drug effects Cell Adhesion Cell Biology Cell Differentiation Enzyme Inhibitors - pharmacology Gene Expression Regulation, Enzymologic - drug effects Humans Life Sciences Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells - cytology Original Paper Osteogenesis - drug effects Pharmacology/Toxicology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Sprague-Dawley Signal Transduction - drug effects Stem cells Tibial Fractures - pathology Tibial Fractures - physiopathology Tibial Fractures - surgery Umbilical Cord - cytology |
| title | AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells |
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