RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells
Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVS...
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| Veröffentlicht in: | PloS one 2011-12, Vol.6 (12), p.e29037 |
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| creator | Yuan, Ling-Qing Zhu, Jia-Hua Wang, Hua-Wen Liang, Qiu-Hua Xie, Hui Wu, Xian-Ping Zhou, Hua Cui, Rong-Rong Sheng, Zhi-Feng Zhou, Hou-De Zhu, Xiao Liu, Guan-Ying Liu, You-Shuo Liao, Er-Yuan |
| description | Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation. |
| doi_str_mv | 10.1371/journal.pone.0029037 |
| format | Article |
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We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0029037</identifier><identifier>PMID: 22194983</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Activation ; AKT protein ; Alkaline phosphatase ; Animals ; Arteriosclerosis ; Arthritis ; Biocompatibility ; Biology ; Calcification ; Calcification (ectopic) ; Cell Differentiation - drug effects ; Cytokines ; Diabetes ; Differentiation ; Endocrinology ; Enzyme Activation - drug effects ; Enzyme inhibitors ; Extracellular signal-regulated kinase ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Gene Expression Regulation - drug effects ; Genetic aspects ; Geriatrics ; Humans ; Inhibitors ; Inositol ; Insulin ; Insulin - pharmacology ; Insulin resistance ; Insulin-like growth factors ; Kinases ; Ligands ; Male ; MAP kinase ; MAP Kinase Signaling System - drug effects ; Medicine ; Metabolism ; Minerals - metabolism ; Mitogens ; Muscle, Smooth, Vascular - cytology ; Muscles ; Myocytes, Smooth Muscle - cytology ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Nodules ; Osteoblastogenesis ; Osteoblasts ; Osteoblasts - cytology ; Osteoblasts - drug effects ; Osteoblasts - enzymology ; Osteocalcin ; Phosphatases ; Physiology ; Pretreatment ; Protein kinase ; Protein kinases ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; RANK Ligand - genetics ; RANK Ligand - metabolism ; Rats ; Rats, Sprague-Dawley ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Secretion ; siRNA ; Smooth muscle ; Threonine ; TRANCE protein ; Type 2 diabetes</subject><ispartof>PloS one, 2011-12, Vol.6 (12), p.e29037</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Yuan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Yuan et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-87a090af1abea0f24b819523c86599cd0ddea14954bbb55b5472e014589e92713</citedby><cites>FETCH-LOGICAL-c757t-87a090af1abea0f24b819523c86599cd0ddea14954bbb55b5472e014589e92713</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/PMC3240644/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240644/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22194983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Agoulnik, Irina</contributor><creatorcontrib>Yuan, Ling-Qing</creatorcontrib><creatorcontrib>Zhu, Jia-Hua</creatorcontrib><creatorcontrib>Wang, Hua-Wen</creatorcontrib><creatorcontrib>Liang, Qiu-Hua</creatorcontrib><creatorcontrib>Xie, Hui</creatorcontrib><creatorcontrib>Wu, Xian-Ping</creatorcontrib><creatorcontrib>Zhou, Hua</creatorcontrib><creatorcontrib>Cui, Rong-Rong</creatorcontrib><creatorcontrib>Sheng, Zhi-Feng</creatorcontrib><creatorcontrib>Zhou, Hou-De</creatorcontrib><creatorcontrib>Zhu, Xiao</creatorcontrib><creatorcontrib>Liu, Guan-Ying</creatorcontrib><creatorcontrib>Liu, You-Shuo</creatorcontrib><creatorcontrib>Liao, Er-Yuan</creatorcontrib><title>RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Activation</subject><subject>AKT protein</subject><subject>Alkaline phosphatase</subject><subject>Animals</subject><subject>Arteriosclerosis</subject><subject>Arthritis</subject><subject>Biocompatibility</subject><subject>Biology</subject><subject>Calcification</subject><subject>Calcification (ectopic)</subject><subject>Cell Differentiation - drug effects</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Differentiation</subject><subject>Endocrinology</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme inhibitors</subject><subject>Extracellular signal-regulated kinase</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genetic aspects</subject><subject>Geriatrics</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Inositol</subject><subject>Insulin</subject><subject>Insulin - pharmacology</subject><subject>Insulin resistance</subject><subject>Insulin-like growth factors</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Male</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Minerals - metabolism</subject><subject>Mitogens</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscles</subject><subject>Myocytes, Smooth Muscle - cytology</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Nodules</subject><subject>Osteoblastogenesis</subject><subject>Osteoblasts</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - enzymology</subject><subject>Osteocalcin</subject><subject>Phosphatases</subject><subject>Physiology</subject><subject>Pretreatment</subject><subject>Protein kinase</subject><subject>Protein kinases</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RANK Ligand - genetics</subject><subject>RANK Ligand - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Secretion</subject><subject>siRNA</subject><subject>Smooth muscle</subject><subject>Threonine</subject><subject>TRANCE protein</subject><subject>Type 2 diabetes</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkluL1DAYhoso7rr6D0QDguBFx5zaNDfCsHgYHFxYD7chSZOZDGkzJu2q_96M012moCAhJHx5vjfJy1sUTxFcIMLQ610YYy_9Yh96s4AQc0jYveIccYLLGkNy_2R_VjxKaQdhRZq6flicYYw45Q05L8L18tPHNXAJSNCGH30aopEd6Ezr5BAisHm6Po3e9aXr21GbFoQ0mKC8TIPToHXWmmj6IfMu9CBYcCOTHr2MIHUhDFvQjUl7A7TxPj0uHljpk3kyrRfF13dvv1x-KNdX71eXy3WpWcWGsmEScigtkspIaDFVDeIVJrqpK851C9vWSER5RZVSVaUqyrCBiFYNNxwzRC6K50fdvQ9JTF4lgQjCiNUI4UysjkQb5E7so-tk_CWCdOJPIcSNkDH_0BthFWMGI1NDZSlRXFGGqMVEaahMg1jWejPdNqpsnc52ROlnovOT3m3FJtwIgimsKc0CLyaBGL6PJg3_ePJEbWR-lettyGK6c0mLJWV1U0NUN5la_IXKozWd0zkt1uX6rOHVrCEzg_k5bOSYklh9vv5_9urbnH15wm6N9MM2BT8ecpLmID2COoaUorF3ziEoDmG_dUMcwi6msOe2Z6eu3zXdppv8BqTW-ws</recordid><startdate>20111215</startdate><enddate>20111215</enddate><creator>Yuan, Ling-Qing</creator><creator>Zhu, Jia-Hua</creator><creator>Wang, Hua-Wen</creator><creator>Liang, Qiu-Hua</creator><creator>Xie, Hui</creator><creator>Wu, Xian-Ping</creator><creator>Zhou, Hua</creator><creator>Cui, Rong-Rong</creator><creator>Sheng, Zhi-Feng</creator><creator>Zhou, Hou-De</creator><creator>Zhu, Xiao</creator><creator>Liu, Guan-Ying</creator><creator>Liu, You-Shuo</creator><creator>Liao, Er-Yuan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111215</creationdate><title>RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells</title><author>Yuan, Ling-Qing ; Zhu, Jia-Hua ; Wang, Hua-Wen ; Liang, Qiu-Hua ; Xie, Hui ; Wu, Xian-Ping ; Zhou, Hua ; Cui, Rong-Rong ; Sheng, Zhi-Feng ; Zhou, Hou-De ; Zhu, Xiao ; Liu, Guan-Ying ; Liu, You-Shuo ; Liao, Er-Yuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-87a090af1abea0f24b819523c86599cd0ddea14954bbb55b5472e014589e92713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Activation</topic><topic>AKT protein</topic><topic>Alkaline phosphatase</topic><topic>Animals</topic><topic>Arteriosclerosis</topic><topic>Arthritis</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Calcification</topic><topic>Calcification (ectopic)</topic><topic>Cell Differentiation - drug effects</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Differentiation</topic><topic>Endocrinology</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme inhibitors</topic><topic>Extracellular signal-regulated kinase</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genetic aspects</topic><topic>Geriatrics</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Inositol</topic><topic>Insulin</topic><topic>Insulin - pharmacology</topic><topic>Insulin resistance</topic><topic>Insulin-like growth factors</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Male</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Medicine</topic><topic>Metabolism</topic><topic>Minerals - metabolism</topic><topic>Mitogens</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscles</topic><topic>Myocytes, Smooth Muscle - cytology</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Nodules</topic><topic>Osteoblastogenesis</topic><topic>Osteoblasts</topic><topic>Osteoblasts - cytology</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - enzymology</topic><topic>Osteocalcin</topic><topic>Phosphatases</topic><topic>Physiology</topic><topic>Pretreatment</topic><topic>Protein kinase</topic><topic>Protein kinases</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RANK Ligand - genetics</topic><topic>RANK Ligand - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Secretion</topic><topic>siRNA</topic><topic>Smooth muscle</topic><topic>Threonine</topic><topic>TRANCE protein</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yuan, Ling-Qing</creatorcontrib><creatorcontrib>Zhu, Jia-Hua</creatorcontrib><creatorcontrib>Wang, Hua-Wen</creatorcontrib><creatorcontrib>Liang, Qiu-Hua</creatorcontrib><creatorcontrib>Xie, Hui</creatorcontrib><creatorcontrib>Wu, Xian-Ping</creatorcontrib><creatorcontrib>Zhou, Hua</creatorcontrib><creatorcontrib>Cui, Rong-Rong</creatorcontrib><creatorcontrib>Sheng, Zhi-Feng</creatorcontrib><creatorcontrib>Zhou, Hou-De</creatorcontrib><creatorcontrib>Zhu, Xiao</creatorcontrib><creatorcontrib>Liu, Guan-Ying</creatorcontrib><creatorcontrib>Liu, You-Shuo</creatorcontrib><creatorcontrib>Liao, Er-Yuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yuan, Ling-Qing</au><au>Zhu, Jia-Hua</au><au>Wang, Hua-Wen</au><au>Liang, Qiu-Hua</au><au>Xie, Hui</au><au>Wu, Xian-Ping</au><au>Zhou, Hua</au><au>Cui, Rong-Rong</au><au>Sheng, Zhi-Feng</au><au>Zhou, Hou-De</au><au>Zhu, Xiao</au><au>Liu, Guan-Ying</au><au>Liu, You-Shuo</au><au>Liao, Er-Yuan</au><au>Agoulnik, Irina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-12-15</date><risdate>2011</risdate><volume>6</volume><issue>12</issue><spage>e29037</spage><pages>e29037-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22194983</pmid><doi>10.1371/journal.pone.0029037</doi><tpages>e29037</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-12, Vol.6 (12), p.e29037 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312176112 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Activation AKT protein Alkaline phosphatase Animals Arteriosclerosis Arthritis Biocompatibility Biology Calcification Calcification (ectopic) Cell Differentiation - drug effects Cytokines Diabetes Differentiation Endocrinology Enzyme Activation - drug effects Enzyme inhibitors Extracellular signal-regulated kinase Extracellular Signal-Regulated MAP Kinases - metabolism Gene Expression Regulation - drug effects Genetic aspects Geriatrics Humans Inhibitors Inositol Insulin Insulin - pharmacology Insulin resistance Insulin-like growth factors Kinases Ligands Male MAP kinase MAP Kinase Signaling System - drug effects Medicine Metabolism Minerals - metabolism Mitogens Muscle, Smooth, Vascular - cytology Muscles Myocytes, Smooth Muscle - cytology Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Nodules Osteoblastogenesis Osteoblasts Osteoblasts - cytology Osteoblasts - drug effects Osteoblasts - enzymology Osteocalcin Phosphatases Physiology Pretreatment Protein kinase Protein kinases Proteins Proto-Oncogene Proteins c-akt - metabolism RANK Ligand - genetics RANK Ligand - metabolism Rats Rats, Sprague-Dawley Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Secretion siRNA Smooth muscle Threonine TRANCE protein Type 2 diabetes |
| title | RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells |
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