Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells
Statins inhibit 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, which catalyzes conversion of HMG‐CoA to mevalonate, a rate‐limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10...
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| Veröffentlicht in: | Journal of cellular biochemistry 2004-06, Vol.92 (3), p.458-471 |
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| creator | Maeda, Toyonobu Matsunuma, Ayako Kurahashi, Izuru Yanagawa, Toru Yoshida, Hiroshi Horiuchi, Noboru |
| description | Statins inhibit 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, which catalyzes conversion of HMG‐CoA to mevalonate, a rate‐limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10−7 M markedly increased mRNA expression for bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3‐E1), while suppressing gene expression for collagenase‐1, and collagenase‐3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase‐digestive proteins, and noncollagenous proteins was increased in the cells treated with 10−7 M simvastatin, or 10−8 M cerivastatin. In the culture of MC3T3‐E1 cells, statins stimulated mineralization; pretreating MC3T3‐E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin‐induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/jcb.20074 |
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The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10−7 M markedly increased mRNA expression for bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3‐E1), while suppressing gene expression for collagenase‐1, and collagenase‐3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase‐digestive proteins, and noncollagenous proteins was increased in the cells treated with 10−7 M simvastatin, or 10−8 M cerivastatin. In the culture of MC3T3‐E1 cells, statins stimulated mineralization; pretreating MC3T3‐E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin‐induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.20074</identifier><identifier>PMID: 15156558</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Alkaline Phosphatase - genetics ; Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Protein 4 ; Bone Morphogenetic Proteins - genetics ; bone sialoprotein ; Calcification, Physiologic - drug effects ; Cell Differentiation - drug effects ; Cell Line ; Collagen - genetics ; Gene Expression Regulation - drug effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Integrin-Binding Sialoprotein ; Mice ; mineralization ; Neoplasm Proteins - genetics ; osteoblast differentiation ; Osteoblasts - cytology ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Osteocalcin - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sialoglycoproteins - genetics ; statins ; Transcription Factors - genetics ; Transforming Growth Factor beta - genetics ; vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics</subject><ispartof>Journal of cellular biochemistry, 2004-06, Vol.92 (3), p.458-471</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4584-ea8b992236a89270c34f15827707b53829a42bb8700eb5f4562ac8633fdb9f943</citedby><cites>FETCH-LOGICAL-c4584-ea8b992236a89270c34f15827707b53829a42bb8700eb5f4562ac8633fdb9f943</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.20074$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.20074$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15156558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maeda, Toyonobu</creatorcontrib><creatorcontrib>Matsunuma, Ayako</creatorcontrib><creatorcontrib>Kurahashi, Izuru</creatorcontrib><creatorcontrib>Yanagawa, Toru</creatorcontrib><creatorcontrib>Yoshida, Hiroshi</creatorcontrib><creatorcontrib>Horiuchi, Noboru</creatorcontrib><title>Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells</title><title>Journal of cellular biochemistry</title><addtitle>J. Cell. Biochem</addtitle><description>Statins inhibit 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, which catalyzes conversion of HMG‐CoA to mevalonate, a rate‐limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10−7 M markedly increased mRNA expression for bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3‐E1), while suppressing gene expression for collagenase‐1, and collagenase‐3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase‐digestive proteins, and noncollagenous proteins was increased in the cells treated with 10−7 M simvastatin, or 10−8 M cerivastatin. In the culture of MC3T3‐E1 cells, statins stimulated mineralization; pretreating MC3T3‐E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin‐induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. © 2004 Wiley‐Liss, Inc.</description><subject>Alkaline Phosphatase - genetics</subject><subject>Animals</subject><subject>Bone Morphogenetic Protein 2</subject><subject>Bone Morphogenetic Protein 4</subject><subject>Bone Morphogenetic Proteins - genetics</subject><subject>bone sialoprotein</subject><subject>Calcification, Physiologic - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line</subject><subject>Collagen - genetics</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Integrin-Binding Sialoprotein</subject><subject>Mice</subject><subject>mineralization</subject><subject>Neoplasm Proteins - genetics</subject><subject>osteoblast differentiation</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Osteocalcin - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sialoglycoproteins - genetics</subject><subject>statins</subject><subject>Transcription Factors - genetics</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctOwzAQRS0EouWx4AdQVkgsQsev2F5CeBUV2BQhsbHsxJYMaVLiVNC_J9ACK8RqpJkzR6M7CB1gOMEAZPRc2BMCINgGGmJQImUZY5toCIJCSigmA7QT4zMAKEXJNhpgjnnGuRyiybguF0UXmjppfNLEzjW2MrFLyuC9a13dBfM1DXUZChcTu0xi17fq2LeS25xOaXqBk8JVVdxDW95U0e2v6y56uLyY5tfp5P5qnJ9O0oJxyVJnpFWKEJoZqYiAgjKPuSRCgLCcSqIMI9ZKAeAs94xnxBQyo9SXVnnF6C46WnnnbfO6cLHTsxA_LzC1axZRC6x6Hab_glgJkmFGevB4BRZtE2PrvJ63YWbapcagPzPWfcb6K-OePVxLF3bmyl9yHWoPjFbAW6jc8m-TvsnPvpXpaiP0D3j_2TDti84EFVw_3l3pJ5ldQz7l-px-ACaXkjs</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>Maeda, Toyonobu</creator><creator>Matsunuma, Ayako</creator><creator>Kurahashi, Izuru</creator><creator>Yanagawa, Toru</creator><creator>Yoshida, Hiroshi</creator><creator>Horiuchi, Noboru</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7QP</scope><scope>7X8</scope></search><sort><creationdate>20040601</creationdate><title>Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells</title><author>Maeda, Toyonobu ; Matsunuma, Ayako ; Kurahashi, Izuru ; Yanagawa, Toru ; Yoshida, Hiroshi ; Horiuchi, Noboru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4584-ea8b992236a89270c34f15827707b53829a42bb8700eb5f4562ac8633fdb9f943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Alkaline Phosphatase - genetics</topic><topic>Animals</topic><topic>Bone Morphogenetic Protein 2</topic><topic>Bone Morphogenetic Protein 4</topic><topic>Bone Morphogenetic Proteins - genetics</topic><topic>bone sialoprotein</topic><topic>Calcification, Physiologic - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line</topic><topic>Collagen - genetics</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Integrin-Binding Sialoprotein</topic><topic>Mice</topic><topic>mineralization</topic><topic>Neoplasm Proteins - genetics</topic><topic>osteoblast differentiation</topic><topic>Osteoblasts - cytology</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Osteocalcin - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sialoglycoproteins - genetics</topic><topic>statins</topic><topic>Transcription Factors - genetics</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maeda, Toyonobu</creatorcontrib><creatorcontrib>Matsunuma, Ayako</creatorcontrib><creatorcontrib>Kurahashi, Izuru</creatorcontrib><creatorcontrib>Yanagawa, Toru</creatorcontrib><creatorcontrib>Yoshida, Hiroshi</creatorcontrib><creatorcontrib>Horiuchi, Noboru</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maeda, Toyonobu</au><au>Matsunuma, Ayako</au><au>Kurahashi, Izuru</au><au>Yanagawa, Toru</au><au>Yoshida, Hiroshi</au><au>Horiuchi, Noboru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. Cell. Biochem</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>92</volume><issue>3</issue><spage>458</spage><epage>471</epage><pages>458-471</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>Statins inhibit 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, which catalyzes conversion of HMG‐CoA to mevalonate, a rate‐limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10−7 M markedly increased mRNA expression for bone morphogenetic protein‐2 (BMP‐2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3‐E1), while suppressing gene expression for collagenase‐1, and collagenase‐3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase‐digestive proteins, and noncollagenous proteins was increased in the cells treated with 10−7 M simvastatin, or 10−8 M cerivastatin. In the culture of MC3T3‐E1 cells, statins stimulated mineralization; pretreating MC3T3‐E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin‐induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15156558</pmid><doi>10.1002/jcb.20074</doi><tpages>14</tpages></addata></record> |
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| subjects | Alkaline Phosphatase - genetics Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins - genetics bone sialoprotein Calcification, Physiologic - drug effects Cell Differentiation - drug effects Cell Line Collagen - genetics Gene Expression Regulation - drug effects Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Integrin-Binding Sialoprotein Mice mineralization Neoplasm Proteins - genetics osteoblast differentiation Osteoblasts - cytology Osteoblasts - drug effects Osteoblasts - metabolism Osteocalcin - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Sialoglycoproteins - genetics statins Transcription Factors - genetics Transforming Growth Factor beta - genetics vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics |
| title | Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells |
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