Interactions between FGF21 and BMP-2 in osteogenesis
► FGF21 enhanced BMP-2-dependent transcription. ► FGF21 enhanced BMP-2-dependent osteogenesis in C2C12 cells. ► FGF21 enhanced BMP-2-dependent Smad pathway. ► BMP-2 negatively regulates FGF21 mRNA expression. Lifestyle-related diseases are increasing and the challenge to create innovative drugs to t...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2013-03, Vol.432 (4), p.677-682 |
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| creator | Ishida, Kazunari Haudenschild, Dominik R. |
| description | ► FGF21 enhanced BMP-2-dependent transcription. ► FGF21 enhanced BMP-2-dependent osteogenesis in C2C12 cells. ► FGF21 enhanced BMP-2-dependent Smad pathway. ► BMP-2 negatively regulates FGF21 mRNA expression.
Lifestyle-related diseases are increasing and the challenge to create innovative drugs to treat such diseases is a main focus in medical science research. Fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism, and is an innovative candidate drug already in clinical trials for type 2 diabetes mellitus and obesity. Bone fragility and impaired fracture healing induced by such lifestyle-related conditions are also a growing problem. Bone morphogenic proteins (BMPs) are well known osteogenic growth factors, and BMP-2 is used to augment bone formation in difficult clinical situations. There are many documented interactions between the FGF and BMP family proteins, although the interaction between FGF21 and BMP-2 remains unknown. The aim of this study was to reveal the effect of FGF21 toward BMP-2-dependent osteogenic activity, using C2C12 cells as a model system. We found that FGF21 enhanced BMP-2-dependent transcription and osteogenesis in the C2C12 cell line, which was confirmed by alkaline phosphatase activity, matrix mineralization, and gene expression. Mechanistically, FGF21 enhanced BMP-2-induced intracellular signaling through Smad proteins, but not through p44/42MAPK proteins. Furthermore, we identified a negative feedback loop in which BMP-2 decreased endogenous FGF21 mRNA expression. In summary, this study demonstrates interactions between BMP-2 and FGF21 pathways exist in vitro, and that FGF21 enhances the osteogenic activity of BMP-2 by up-regulating the BMP-2-dependent Smad signaling pathway. |
| doi_str_mv | 10.1016/j.bbrc.2013.02.019 |
| format | Article |
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Lifestyle-related diseases are increasing and the challenge to create innovative drugs to treat such diseases is a main focus in medical science research. Fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism, and is an innovative candidate drug already in clinical trials for type 2 diabetes mellitus and obesity. Bone fragility and impaired fracture healing induced by such lifestyle-related conditions are also a growing problem. Bone morphogenic proteins (BMPs) are well known osteogenic growth factors, and BMP-2 is used to augment bone formation in difficult clinical situations. There are many documented interactions between the FGF and BMP family proteins, although the interaction between FGF21 and BMP-2 remains unknown. The aim of this study was to reveal the effect of FGF21 toward BMP-2-dependent osteogenic activity, using C2C12 cells as a model system. We found that FGF21 enhanced BMP-2-dependent transcription and osteogenesis in the C2C12 cell line, which was confirmed by alkaline phosphatase activity, matrix mineralization, and gene expression. Mechanistically, FGF21 enhanced BMP-2-induced intracellular signaling through Smad proteins, but not through p44/42MAPK proteins. Furthermore, we identified a negative feedback loop in which BMP-2 decreased endogenous FGF21 mRNA expression. In summary, this study demonstrates interactions between BMP-2 and FGF21 pathways exist in vitro, and that FGF21 enhances the osteogenic activity of BMP-2 by up-regulating the BMP-2-dependent Smad signaling pathway.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2013.02.019</identifier><identifier>PMID: 23416071</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Bone Morphogenetic Protein 2 - metabolism ; Bone morphogenic protein-2 ; Cell Line ; Chondrocytes - metabolism ; Fibroblast growth factor 21 ; Fibroblast Growth Factors - genetics ; Fibroblast Growth Factors - metabolism ; Gene Expression Regulation ; Humans ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Osteogenesis ; Osteogenesis - genetics ; Osteogenesis - physiology ; Phosphorylation ; Smad pathway ; Smad1 Protein - metabolism ; Smad5 Protein - metabolism ; Smad8 Protein - metabolism ; Transcription, Genetic</subject><ispartof>Biochemical and biophysical research communications, 2013-03, Vol.432 (4), p.677-682</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-76a7249d19bda7fe6d6e16d4ca5ff898fb3945e5b987aa6246ba0fa97b65c0b83</citedby><cites>FETCH-LOGICAL-c455t-76a7249d19bda7fe6d6e16d4ca5ff898fb3945e5b987aa6246ba0fa97b65c0b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2013.02.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23416071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ishida, Kazunari</creatorcontrib><creatorcontrib>Haudenschild, Dominik R.</creatorcontrib><title>Interactions between FGF21 and BMP-2 in osteogenesis</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>► FGF21 enhanced BMP-2-dependent transcription. ► FGF21 enhanced BMP-2-dependent osteogenesis in C2C12 cells. ► FGF21 enhanced BMP-2-dependent Smad pathway. ► BMP-2 negatively regulates FGF21 mRNA expression.
Lifestyle-related diseases are increasing and the challenge to create innovative drugs to treat such diseases is a main focus in medical science research. Fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism, and is an innovative candidate drug already in clinical trials for type 2 diabetes mellitus and obesity. Bone fragility and impaired fracture healing induced by such lifestyle-related conditions are also a growing problem. Bone morphogenic proteins (BMPs) are well known osteogenic growth factors, and BMP-2 is used to augment bone formation in difficult clinical situations. There are many documented interactions between the FGF and BMP family proteins, although the interaction between FGF21 and BMP-2 remains unknown. The aim of this study was to reveal the effect of FGF21 toward BMP-2-dependent osteogenic activity, using C2C12 cells as a model system. We found that FGF21 enhanced BMP-2-dependent transcription and osteogenesis in the C2C12 cell line, which was confirmed by alkaline phosphatase activity, matrix mineralization, and gene expression. Mechanistically, FGF21 enhanced BMP-2-induced intracellular signaling through Smad proteins, but not through p44/42MAPK proteins. Furthermore, we identified a negative feedback loop in which BMP-2 decreased endogenous FGF21 mRNA expression. In summary, this study demonstrates interactions between BMP-2 and FGF21 pathways exist in vitro, and that FGF21 enhances the osteogenic activity of BMP-2 by up-regulating the BMP-2-dependent Smad signaling pathway.</description><subject>Bone Morphogenetic Protein 2 - metabolism</subject><subject>Bone morphogenic protein-2</subject><subject>Cell Line</subject><subject>Chondrocytes - metabolism</subject><subject>Fibroblast growth factor 21</subject><subject>Fibroblast Growth Factors - genetics</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Osteogenesis</subject><subject>Osteogenesis - genetics</subject><subject>Osteogenesis - physiology</subject><subject>Phosphorylation</subject><subject>Smad pathway</subject><subject>Smad1 Protein - metabolism</subject><subject>Smad5 Protein - metabolism</subject><subject>Smad8 Protein - metabolism</subject><subject>Transcription, Genetic</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkLFOwzAURS0EoqXwAwwoI0vCe47jxBILIAqVimAAic2ynRfkqk3ATkH8PakKjIjpLuee4TB2jJAhoDxbZNYGl3HAPAOeAaodNkZQkHIEscvGACBTrvB5xA5iXAAgCqn22YjnAiWUOGZi1vYUjOt918bEUv9B1CbTmynHxLR1cnn3kPLEt0kXe-peqKXo4yHba8wy0tH3TtjT9Prx6jad39_Mri7mqRNF0aelNCUXqkZla1M2JGtJKGvhTNE0laoamytRUGFVVRojuZDWQGNUaWXhwFb5hJ1uva-he1tT7PXKR0fLpWmpW0eNecF5xVHiP1BUEksBakD5FnWhizFQo1-DX5nwqRH0Jqxe6E1YvQmrgesh7HA6-fav7Yrq38tPyQE43wI0BHn3FHR0nlpHtQ_kel13_i__F4TvhvA</recordid><startdate>20130322</startdate><enddate>20130322</enddate><creator>Ishida, Kazunari</creator><creator>Haudenschild, Dominik R.</creator><general>Elsevier Inc</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>7X8</scope><scope>7QP</scope></search><sort><creationdate>20130322</creationdate><title>Interactions between FGF21 and BMP-2 in osteogenesis</title><author>Ishida, Kazunari ; Haudenschild, Dominik R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-76a7249d19bda7fe6d6e16d4ca5ff898fb3945e5b987aa6246ba0fa97b65c0b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Bone Morphogenetic Protein 2 - metabolism</topic><topic>Bone morphogenic protein-2</topic><topic>Cell Line</topic><topic>Chondrocytes - metabolism</topic><topic>Fibroblast growth factor 21</topic><topic>Fibroblast Growth Factors - genetics</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Osteogenesis</topic><topic>Osteogenesis - genetics</topic><topic>Osteogenesis - physiology</topic><topic>Phosphorylation</topic><topic>Smad pathway</topic><topic>Smad1 Protein - metabolism</topic><topic>Smad5 Protein - metabolism</topic><topic>Smad8 Protein - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishida, Kazunari</creatorcontrib><creatorcontrib>Haudenschild, Dominik R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishida, Kazunari</au><au>Haudenschild, Dominik R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interactions between FGF21 and BMP-2 in osteogenesis</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2013-03-22</date><risdate>2013</risdate><volume>432</volume><issue>4</issue><spage>677</spage><epage>682</epage><pages>677-682</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>► FGF21 enhanced BMP-2-dependent transcription. ► FGF21 enhanced BMP-2-dependent osteogenesis in C2C12 cells. ► FGF21 enhanced BMP-2-dependent Smad pathway. ► BMP-2 negatively regulates FGF21 mRNA expression.
Lifestyle-related diseases are increasing and the challenge to create innovative drugs to treat such diseases is a main focus in medical science research. Fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism, and is an innovative candidate drug already in clinical trials for type 2 diabetes mellitus and obesity. Bone fragility and impaired fracture healing induced by such lifestyle-related conditions are also a growing problem. Bone morphogenic proteins (BMPs) are well known osteogenic growth factors, and BMP-2 is used to augment bone formation in difficult clinical situations. There are many documented interactions between the FGF and BMP family proteins, although the interaction between FGF21 and BMP-2 remains unknown. The aim of this study was to reveal the effect of FGF21 toward BMP-2-dependent osteogenic activity, using C2C12 cells as a model system. We found that FGF21 enhanced BMP-2-dependent transcription and osteogenesis in the C2C12 cell line, which was confirmed by alkaline phosphatase activity, matrix mineralization, and gene expression. Mechanistically, FGF21 enhanced BMP-2-induced intracellular signaling through Smad proteins, but not through p44/42MAPK proteins. Furthermore, we identified a negative feedback loop in which BMP-2 decreased endogenous FGF21 mRNA expression. In summary, this study demonstrates interactions between BMP-2 and FGF21 pathways exist in vitro, and that FGF21 enhances the osteogenic activity of BMP-2 by up-regulating the BMP-2-dependent Smad signaling pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23416071</pmid><doi>10.1016/j.bbrc.2013.02.019</doi><tpages>6</tpages></addata></record> |
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| subjects | Bone Morphogenetic Protein 2 - metabolism Bone morphogenic protein-2 Cell Line Chondrocytes - metabolism Fibroblast growth factor 21 Fibroblast Growth Factors - genetics Fibroblast Growth Factors - metabolism Gene Expression Regulation Humans Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Osteogenesis Osteogenesis - genetics Osteogenesis - physiology Phosphorylation Smad pathway Smad1 Protein - metabolism Smad5 Protein - metabolism Smad8 Protein - metabolism Transcription, Genetic |
| title | Interactions between FGF21 and BMP-2 in osteogenesis |
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