Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma
Growth and differentiation factor 11 (GDF11) is a TGF-β family member that is expressed widely and plays multiple roles, including regulating axial skeletal patterning during development. However, the function of GDF11 in the bone is barely understood. Here we identify GDF11 as a potent regulator of...
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| Veröffentlicht in: | Gene 2015-02, Vol.557 (2), p.209-214 |
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| creator | Zhang, Yan Shao, Jin Wang, Zhi Yang, Tieyi Liu, Shuyi Liu, Yue Fan, Xinbing Ye, Weiguang |
| description | Growth and differentiation factor 11 (GDF11) is a TGF-β family member that is expressed widely and plays multiple roles, including regulating axial skeletal patterning during development. However, the function of GDF11 in the bone is barely understood. Here we identify GDF11 as a potent regulator of bone homeostasis. GDF11 level is significantly decreased in the plasma and bone marrow of aging mice and mice with osteoporosis. Pharmacologic GDF11 gain of function leads to a striking increase in osteoblastogenesis and inhibits adipogenesis from bone marrow mesenchymal stem cells by altering the gene expression pattern. GDF11 inhibits the activity of the peroxisome proliferator-activated receptor γ (PPAR-γ) by promoting its SUMOylation. Therefore, GDF11 is a critical rheostat for bone turnover and a key integrator of bone homeostasis. These results reveal that skeletal fragility may be reduced by chronic GDF11 administration.
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•GDF11 is decreased during osteoporosis in human and mice.•GDF11 induces osteoblastogenesis and related gene expression.•GDF11 inhibits adipogenesis and related gene expression.•GDF11 inhibits the expression of PPAR-γ by SUMOylation. |
| doi_str_mv | 10.1016/j.gene.2014.12.039 |
| format | Article |
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[Display omitted]
•GDF11 is decreased during osteoporosis in human and mice.•GDF11 induces osteoblastogenesis and related gene expression.•GDF11 inhibits adipogenesis and related gene expression.•GDF11 inhibits the expression of PPAR-γ by SUMOylation.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2014.12.039</identifier><identifier>PMID: 25534870</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adipogenesis ; Animals ; Bone Morphogenetic Proteins - genetics ; Bone Morphogenetic Proteins - metabolism ; Female ; GDF11 ; Gene Expression ; Growth Differentiation Factors - genetics ; Growth Differentiation Factors - metabolism ; Humans ; Mice, Inbred C57BL ; Middle Aged ; Osteoblastogenesis ; Osteoblasts - physiology ; Osteoporosis ; Osteoporosis - metabolism ; PPAR gamma - genetics ; PPAR gamma - metabolism ; PPAR-γ ; Sumoylation</subject><ispartof>Gene, 2015-02, Vol.557 (2), p.209-214</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-c9e175535688fc9a4e96f0858af3708cbbcb972f7b28e29b9eb4ce645b80775b3</citedby><cites>FETCH-LOGICAL-c459t-c9e175535688fc9a4e96f0858af3708cbbcb972f7b28e29b9eb4ce645b80775b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.gene.2014.12.039$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25534870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Shao, Jin</creatorcontrib><creatorcontrib>Wang, Zhi</creatorcontrib><creatorcontrib>Yang, Tieyi</creatorcontrib><creatorcontrib>Liu, Shuyi</creatorcontrib><creatorcontrib>Liu, Yue</creatorcontrib><creatorcontrib>Fan, Xinbing</creatorcontrib><creatorcontrib>Ye, Weiguang</creatorcontrib><title>Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma</title><title>Gene</title><addtitle>Gene</addtitle><description>Growth and differentiation factor 11 (GDF11) is a TGF-β family member that is expressed widely and plays multiple roles, including regulating axial skeletal patterning during development. However, the function of GDF11 in the bone is barely understood. Here we identify GDF11 as a potent regulator of bone homeostasis. GDF11 level is significantly decreased in the plasma and bone marrow of aging mice and mice with osteoporosis. Pharmacologic GDF11 gain of function leads to a striking increase in osteoblastogenesis and inhibits adipogenesis from bone marrow mesenchymal stem cells by altering the gene expression pattern. GDF11 inhibits the activity of the peroxisome proliferator-activated receptor γ (PPAR-γ) by promoting its SUMOylation. Therefore, GDF11 is a critical rheostat for bone turnover and a key integrator of bone homeostasis. These results reveal that skeletal fragility may be reduced by chronic GDF11 administration.
[Display omitted]
•GDF11 is decreased during osteoporosis in human and mice.•GDF11 induces osteoblastogenesis and related gene expression.•GDF11 inhibits adipogenesis and related gene expression.•GDF11 inhibits the expression of PPAR-γ by SUMOylation.</description><subject>Adipogenesis</subject><subject>Animals</subject><subject>Bone Morphogenetic Proteins - genetics</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Female</subject><subject>GDF11</subject><subject>Gene Expression</subject><subject>Growth Differentiation Factors - genetics</subject><subject>Growth Differentiation Factors - metabolism</subject><subject>Humans</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Osteoblastogenesis</subject><subject>Osteoblasts - physiology</subject><subject>Osteoporosis</subject><subject>Osteoporosis - metabolism</subject><subject>PPAR gamma - genetics</subject><subject>PPAR gamma - metabolism</subject><subject>PPAR-γ</subject><subject>Sumoylation</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV1LBCEYhSWK2j7-QBcxl93MpM44KnQT0RcERdS1qPu6ueyMpe5G_z6XrS4jQbzweQ_nPQehY4Ibgkl_Nm9mMEJDMekaQhvcyi00IYLLGuNWbKMJbrmoCSFyD-2nNMflMEZ30R5lrO0ExxMENzF85Ndq6p2DCGP2OvswVk7bHGJFSOVTpau3GDLY7Ffw8-PKDSlDMAudclg7SQU1n1XWcQbZj7Pq8fHiaaaHQR-iHacXCY6-3wP0cn31fHlb3z_c3F1e3Ne2YzLXVgLhxRrrhXBW6g5k77BgQruWY2GNsUZy6rihAqg0Ekxnoe-YEZhzZtoDdLrRLX7fl5CyGnyysFjoEcIyKdL3ghZ9Kv-BMtoKgTtcULpBbQwpRXDqLfpBx09FsFo3oeZqvb9aN6EIVaWJMnTyrb80A0x_R36iL8D5BoASyMpDVMl6GC1MfSxRq2nwf-l_Ac9lmm0</recordid><startdate>20150225</startdate><enddate>20150225</enddate><creator>Zhang, Yan</creator><creator>Shao, Jin</creator><creator>Wang, Zhi</creator><creator>Yang, Tieyi</creator><creator>Liu, Shuyi</creator><creator>Liu, Yue</creator><creator>Fan, Xinbing</creator><creator>Ye, Weiguang</creator><general>Elsevier B.V</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20150225</creationdate><title>Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma</title><author>Zhang, Yan ; Shao, Jin ; Wang, Zhi ; Yang, Tieyi ; Liu, Shuyi ; Liu, Yue ; Fan, Xinbing ; Ye, Weiguang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-c9e175535688fc9a4e96f0858af3708cbbcb972f7b28e29b9eb4ce645b80775b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adipogenesis</topic><topic>Animals</topic><topic>Bone Morphogenetic Proteins - genetics</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>Female</topic><topic>GDF11</topic><topic>Gene Expression</topic><topic>Growth Differentiation Factors - genetics</topic><topic>Growth Differentiation Factors - metabolism</topic><topic>Humans</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Osteoblastogenesis</topic><topic>Osteoblasts - physiology</topic><topic>Osteoporosis</topic><topic>Osteoporosis - metabolism</topic><topic>PPAR gamma - genetics</topic><topic>PPAR gamma - metabolism</topic><topic>PPAR-γ</topic><topic>Sumoylation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Shao, Jin</creatorcontrib><creatorcontrib>Wang, Zhi</creatorcontrib><creatorcontrib>Yang, Tieyi</creatorcontrib><creatorcontrib>Liu, Shuyi</creatorcontrib><creatorcontrib>Liu, Yue</creatorcontrib><creatorcontrib>Fan, Xinbing</creatorcontrib><creatorcontrib>Ye, Weiguang</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yan</au><au>Shao, Jin</au><au>Wang, Zhi</au><au>Yang, Tieyi</au><au>Liu, Shuyi</au><au>Liu, Yue</au><au>Fan, Xinbing</au><au>Ye, Weiguang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2015-02-25</date><risdate>2015</risdate><volume>557</volume><issue>2</issue><spage>209</spage><epage>214</epage><pages>209-214</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>Growth and differentiation factor 11 (GDF11) is a TGF-β family member that is expressed widely and plays multiple roles, including regulating axial skeletal patterning during development. However, the function of GDF11 in the bone is barely understood. Here we identify GDF11 as a potent regulator of bone homeostasis. GDF11 level is significantly decreased in the plasma and bone marrow of aging mice and mice with osteoporosis. Pharmacologic GDF11 gain of function leads to a striking increase in osteoblastogenesis and inhibits adipogenesis from bone marrow mesenchymal stem cells by altering the gene expression pattern. GDF11 inhibits the activity of the peroxisome proliferator-activated receptor γ (PPAR-γ) by promoting its SUMOylation. Therefore, GDF11 is a critical rheostat for bone turnover and a key integrator of bone homeostasis. These results reveal that skeletal fragility may be reduced by chronic GDF11 administration.
[Display omitted]
•GDF11 is decreased during osteoporosis in human and mice.•GDF11 induces osteoblastogenesis and related gene expression.•GDF11 inhibits adipogenesis and related gene expression.•GDF11 inhibits the expression of PPAR-γ by SUMOylation.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25534870</pmid><doi>10.1016/j.gene.2014.12.039</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Adipogenesis Animals Bone Morphogenetic Proteins - genetics Bone Morphogenetic Proteins - metabolism Female GDF11 Gene Expression Growth Differentiation Factors - genetics Growth Differentiation Factors - metabolism Humans Mice, Inbred C57BL Middle Aged Osteoblastogenesis Osteoblasts - physiology Osteoporosis Osteoporosis - metabolism PPAR gamma - genetics PPAR gamma - metabolism PPAR-γ Sumoylation |
| title | Growth differentiation factor 11 is a protective factor for osteoblastogenesis by targeting PPARgamma |
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