Serum IGF‐1 Determines Skeletal Strength by Regulating Subperiosteal Expansion and Trait Interactions
Strong correlations between serum IGF‐1 levels and fracture risk indicate that IGF‐1 plays a critical role in regulating bone strength. However, the mechanism by which serum IGF‐1 regulates bone structure and fracture resistance remains obscure and cannot be determined using conventional approaches....
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Veröffentlicht in: | Journal of bone and mineral research 2009-08, Vol.24 (8), p.1481-1492 |
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creator | Yakar, Shoshana Canalis, Ernesto Sun, Hui Mejia, Wilson Kawashima, Yuki Nasser, Philip Courtland, Hayden‐William Williams, Valerie Bouxsein, Mary Rosen, Clifford Jepsen, Karl J |
description | Strong correlations between serum IGF‐1 levels and fracture risk indicate that IGF‐1 plays a critical role in regulating bone strength. However, the mechanism by which serum IGF‐1 regulates bone structure and fracture resistance remains obscure and cannot be determined using conventional approaches. Previous analysis of adult liver‐specific IGF‐1–deficient (LID) mice, which exhibit 75% reductions in serum IGF‐1 levels, showed reductions in periosteal circumference, femoral cross‐sectional area, cortical thickness, and total volumetric BMD. Understanding the developmental sequences and the resultant anatomical changes that led to this adult phenotype is the key for understanding the complex relationship between serum IGF‐1 levels and fracture risk. Here, we identified a unique developmental pattern of morphological and compositional traits that contribute to bone strength. We show that reduced bone strength associated with low levels of IGF‐1 in serum (LID mice) result in impaired subperiosteal expansion combined with impaired endosteal apposition and lack of compensatory changes in mineralization throughout growth and aging. We show that serum IGF‐1 affects cellular activity differently depending on the cortical surface. Last, we show that chronic reductions in serum IGF‐1 indirectly affect bone strength through its effect on the marrow myeloid progenitor cell population. We conclude that serum IGF‐1 not only regulates bone size, shape, and composition during ontogeny, but it plays a more fundamental role—that of regulating an individual's ability to adapt its bone structure to mechanical loads during growth and development. |
doi_str_mv | 10.1359/jbmr.090226 |
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However, the mechanism by which serum IGF‐1 regulates bone structure and fracture resistance remains obscure and cannot be determined using conventional approaches. Previous analysis of adult liver‐specific IGF‐1–deficient (LID) mice, which exhibit 75% reductions in serum IGF‐1 levels, showed reductions in periosteal circumference, femoral cross‐sectional area, cortical thickness, and total volumetric BMD. Understanding the developmental sequences and the resultant anatomical changes that led to this adult phenotype is the key for understanding the complex relationship between serum IGF‐1 levels and fracture risk. Here, we identified a unique developmental pattern of morphological and compositional traits that contribute to bone strength. We show that reduced bone strength associated with low levels of IGF‐1 in serum (LID mice) result in impaired subperiosteal expansion combined with impaired endosteal apposition and lack of compensatory changes in mineralization throughout growth and aging. We show that serum IGF‐1 affects cellular activity differently depending on the cortical surface. Last, we show that chronic reductions in serum IGF‐1 indirectly affect bone strength through its effect on the marrow myeloid progenitor cell population. We conclude that serum IGF‐1 not only regulates bone size, shape, and composition during ontogeny, but it plays a more fundamental role—that of regulating an individual's ability to adapt its bone structure to mechanical loads during growth and development.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1359/jbmr.090226</identifier><identifier>PMID: 19257833</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>Washington, DC: John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</publisher><subject>acid labile subunit ; Animals ; binding proteins ; Biological and medical sciences ; Body Composition ; Body Weight ; Bone and Bones - diagnostic imaging ; Bone and Bones - physiology ; Bone Density ; bone fragility ; bone strength ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; functional adaptation ; Fundamental and applied biological sciences. Psychology ; IGF ; Insulin Resistance ; Insulin-Like Growth Factor I - metabolism ; Mice ; Original ; osteoblast ; osteoclast ; Periosteum - growth & development ; Radioimmunoassay ; Skeleton and joints ; Tomography, X-Ray Computed ; Vertebrates: osteoarticular system, musculoskeletal system</subject><ispartof>Journal of bone and mineral research, 2009-08, Vol.24 (8), p.1481-1492</ispartof><rights>Copyright © 2009 ASBMR</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 by the American Society for Bone and Mineral Research 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4886-3d3470d74097feb987f4af41a94940c6d8f970df507e5de5b2b89bd58a8358263</citedby><cites>FETCH-LOGICAL-c4886-3d3470d74097feb987f4af41a94940c6d8f970df507e5de5b2b89bd58a8358263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1359%2Fjbmr.090226$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1359%2Fjbmr.090226$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21830906$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19257833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yakar, Shoshana</creatorcontrib><creatorcontrib>Canalis, Ernesto</creatorcontrib><creatorcontrib>Sun, Hui</creatorcontrib><creatorcontrib>Mejia, Wilson</creatorcontrib><creatorcontrib>Kawashima, Yuki</creatorcontrib><creatorcontrib>Nasser, Philip</creatorcontrib><creatorcontrib>Courtland, Hayden‐William</creatorcontrib><creatorcontrib>Williams, Valerie</creatorcontrib><creatorcontrib>Bouxsein, Mary</creatorcontrib><creatorcontrib>Rosen, Clifford</creatorcontrib><creatorcontrib>Jepsen, Karl J</creatorcontrib><title>Serum IGF‐1 Determines Skeletal Strength by Regulating Subperiosteal Expansion and Trait Interactions</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>Strong correlations between serum IGF‐1 levels and fracture risk indicate that IGF‐1 plays a critical role in regulating bone strength. However, the mechanism by which serum IGF‐1 regulates bone structure and fracture resistance remains obscure and cannot be determined using conventional approaches. Previous analysis of adult liver‐specific IGF‐1–deficient (LID) mice, which exhibit 75% reductions in serum IGF‐1 levels, showed reductions in periosteal circumference, femoral cross‐sectional area, cortical thickness, and total volumetric BMD. Understanding the developmental sequences and the resultant anatomical changes that led to this adult phenotype is the key for understanding the complex relationship between serum IGF‐1 levels and fracture risk. Here, we identified a unique developmental pattern of morphological and compositional traits that contribute to bone strength. We show that reduced bone strength associated with low levels of IGF‐1 in serum (LID mice) result in impaired subperiosteal expansion combined with impaired endosteal apposition and lack of compensatory changes in mineralization throughout growth and aging. We show that serum IGF‐1 affects cellular activity differently depending on the cortical surface. Last, we show that chronic reductions in serum IGF‐1 indirectly affect bone strength through its effect on the marrow myeloid progenitor cell population. We conclude that serum IGF‐1 not only regulates bone size, shape, and composition during ontogeny, but it plays a more fundamental role—that of regulating an individual's ability to adapt its bone structure to mechanical loads during growth and development.</description><subject>acid labile subunit</subject><subject>Animals</subject><subject>binding proteins</subject><subject>Biological and medical sciences</subject><subject>Body Composition</subject><subject>Body Weight</subject><subject>Bone and Bones - diagnostic imaging</subject><subject>Bone and Bones - physiology</subject><subject>Bone Density</subject><subject>bone fragility</subject><subject>bone strength</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Flow Cytometry</subject><subject>functional adaptation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>IGF</subject><subject>Insulin Resistance</subject><subject>Insulin-Like Growth Factor I - metabolism</subject><subject>Mice</subject><subject>Original</subject><subject>osteoblast</subject><subject>osteoclast</subject><subject>Periosteum - growth & development</subject><subject>Radioimmunoassay</subject><subject>Skeleton and joints</subject><subject>Tomography, X-Ray Computed</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQhy0EokvhxB35AheU1v_tXJCgtGWrIqRuOVtOMkldEmexHWBvPALPyJOQ1a4KXOA00synb2b0Q-gpJUeUy_L4thriESkJY-oeWlDJeCGUoffRghgjCiI4PUCPUrolhCip1EN0QEsmteF8gboVxGnAy_Ozn99_UPwWMsTBB0h49Ql6yK7HqxwhdPkGVxt8Bd3Uu-xDh1dTtYbox5Rhhk6_rV1IfgzYhQZfR-czXoZZ5uo8d9Nj9KB1fYIn-3qIPp6dXp-8Ky4_nC9PXl8WtTBGFbzhQpNGC1LqFqrS6Fa4VlBXilKQWjWmLed5K4kG2YCsWGXKqpHGGS4NU_wQvdp511M1QFNDyNH1dh394OLGjs7bvyfB39hu_GKZpsYQMgte7AVx_DxBynbwqYa-dwHGKVmlpeTzqf8FGdFEUr41vtyBdRxTitDeXUOJ3SZotwnaXYIz_ezPB36z-8hm4PkecKl2fRtdqH264xg1fFZtRXrHffU9bP610168eX8llSRMEEMV_wUzFLc4</recordid><startdate>200908</startdate><enddate>200908</enddate><creator>Yakar, Shoshana</creator><creator>Canalis, Ernesto</creator><creator>Sun, Hui</creator><creator>Mejia, Wilson</creator><creator>Kawashima, Yuki</creator><creator>Nasser, Philip</creator><creator>Courtland, Hayden‐William</creator><creator>Williams, Valerie</creator><creator>Bouxsein, Mary</creator><creator>Rosen, Clifford</creator><creator>Jepsen, Karl J</creator><general>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</general><general>Wiley</general><general>Amer Soc Bone & Mineral Res</general><scope>IQODW</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><scope>5PM</scope></search><sort><creationdate>200908</creationdate><title>Serum IGF‐1 Determines Skeletal Strength by Regulating Subperiosteal Expansion and Trait Interactions</title><author>Yakar, Shoshana ; Canalis, Ernesto ; Sun, Hui ; Mejia, Wilson ; Kawashima, Yuki ; Nasser, Philip ; Courtland, Hayden‐William ; Williams, Valerie ; Bouxsein, Mary ; Rosen, Clifford ; Jepsen, Karl J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4886-3d3470d74097feb987f4af41a94940c6d8f970df507e5de5b2b89bd58a8358263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>acid labile subunit</topic><topic>Animals</topic><topic>binding proteins</topic><topic>Biological and medical sciences</topic><topic>Body Composition</topic><topic>Body Weight</topic><topic>Bone and Bones - diagnostic imaging</topic><topic>Bone and Bones - physiology</topic><topic>Bone Density</topic><topic>bone fragility</topic><topic>bone strength</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Flow Cytometry</topic><topic>functional adaptation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>IGF</topic><topic>Insulin Resistance</topic><topic>Insulin-Like Growth Factor I - metabolism</topic><topic>Mice</topic><topic>Original</topic><topic>osteoblast</topic><topic>osteoclast</topic><topic>Periosteum - growth & development</topic><topic>Radioimmunoassay</topic><topic>Skeleton and joints</topic><topic>Tomography, X-Ray Computed</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yakar, Shoshana</creatorcontrib><creatorcontrib>Canalis, Ernesto</creatorcontrib><creatorcontrib>Sun, Hui</creatorcontrib><creatorcontrib>Mejia, Wilson</creatorcontrib><creatorcontrib>Kawashima, Yuki</creatorcontrib><creatorcontrib>Nasser, Philip</creatorcontrib><creatorcontrib>Courtland, Hayden‐William</creatorcontrib><creatorcontrib>Williams, Valerie</creatorcontrib><creatorcontrib>Bouxsein, Mary</creatorcontrib><creatorcontrib>Rosen, Clifford</creatorcontrib><creatorcontrib>Jepsen, Karl J</creatorcontrib><collection>Pascal-Francis</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yakar, Shoshana</au><au>Canalis, Ernesto</au><au>Sun, Hui</au><au>Mejia, Wilson</au><au>Kawashima, Yuki</au><au>Nasser, Philip</au><au>Courtland, Hayden‐William</au><au>Williams, Valerie</au><au>Bouxsein, Mary</au><au>Rosen, Clifford</au><au>Jepsen, Karl J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum IGF‐1 Determines Skeletal Strength by Regulating Subperiosteal Expansion and Trait Interactions</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2009-08</date><risdate>2009</risdate><volume>24</volume><issue>8</issue><spage>1481</spage><epage>1492</epage><pages>1481-1492</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>Strong correlations between serum IGF‐1 levels and fracture risk indicate that IGF‐1 plays a critical role in regulating bone strength. However, the mechanism by which serum IGF‐1 regulates bone structure and fracture resistance remains obscure and cannot be determined using conventional approaches. Previous analysis of adult liver‐specific IGF‐1–deficient (LID) mice, which exhibit 75% reductions in serum IGF‐1 levels, showed reductions in periosteal circumference, femoral cross‐sectional area, cortical thickness, and total volumetric BMD. Understanding the developmental sequences and the resultant anatomical changes that led to this adult phenotype is the key for understanding the complex relationship between serum IGF‐1 levels and fracture risk. Here, we identified a unique developmental pattern of morphological and compositional traits that contribute to bone strength. We show that reduced bone strength associated with low levels of IGF‐1 in serum (LID mice) result in impaired subperiosteal expansion combined with impaired endosteal apposition and lack of compensatory changes in mineralization throughout growth and aging. We show that serum IGF‐1 affects cellular activity differently depending on the cortical surface. Last, we show that chronic reductions in serum IGF‐1 indirectly affect bone strength through its effect on the marrow myeloid progenitor cell population. We conclude that serum IGF‐1 not only regulates bone size, shape, and composition during ontogeny, but it plays a more fundamental role—that of regulating an individual's ability to adapt its bone structure to mechanical loads during growth and development.</abstract><cop>Washington, DC</cop><pub>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</pub><pmid>19257833</pmid><doi>10.1359/jbmr.090226</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | acid labile subunit Animals binding proteins Biological and medical sciences Body Composition Body Weight Bone and Bones - diagnostic imaging Bone and Bones - physiology Bone Density bone fragility bone strength Enzyme-Linked Immunosorbent Assay Flow Cytometry functional adaptation Fundamental and applied biological sciences. Psychology IGF Insulin Resistance Insulin-Like Growth Factor I - metabolism Mice Original osteoblast osteoclast Periosteum - growth & development Radioimmunoassay Skeleton and joints Tomography, X-Ray Computed Vertebrates: osteoarticular system, musculoskeletal system |
title | Serum IGF‐1 Determines Skeletal Strength by Regulating Subperiosteal Expansion and Trait Interactions |
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