Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture
Abstract Notch receptors regulate cell differentiation and function. Notch1 and Notch2 inactivation in osteoblasts and osteocytes increases cancellous bone volume, but the function of Notch signaling in osteoblast precursors is unknown. To inactivate Notch signaling in immature osteoblastic cells, m...
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| Veröffentlicht in: | Bone (New York, N.Y.) N.Y.), 2014-05, Vol.62, p.22-28 |
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| description | Abstract Notch receptors regulate cell differentiation and function. Notch1 and Notch2 inactivation in osteoblasts and osteocytes increases cancellous bone volume, but the function of Notch signaling in osteoblast precursors is unknown. To inactivate Notch signaling in immature osteoblastic cells, mice homozygous for conditional Notch1 and Notch2 alleles ( Notch1loxP/loxP ;Notch2loxP/loxP ) were crossed with mice where the osterix ( Osx ) promoter, regulated by a Tet-Off cassette, governs Cre expression ( Osx-Cre ). Notch1loxP/loxP ;Notch2loxP/loxP control and Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ experimental littermate cohorts were obtained. To prevent the effects of embryonic Osx-Cre expression, doxycycline was administered to pregnant dams, but not to newborns. Recombination of conditional alleles was documented in calvarial DNA extracts from 1 month old mice. Notch1 and Notch2 inactivation did not affect femoral microarchitecture at 1 month of age. Cancellous bone volume was higher and structure model index was lower in 3 and 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ mice than in control littermates and the effect was more pronounced in female mice. One month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ male mice transiently exhibited an increase in osteoblast number and a modest suppression in bone resorption. Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice displayed a tendency toward increased bone formation at 3 months of age, although bone remodeling was suppressed in 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice. Notch1 and Notch2 inactivation increased porosity and reduced thickness of cortical bone. These effects were modest and more evident in 3 and 6 month old female than in male mice of the same age. In conclusion, Notch1 and Notch2 expression in osteoblast precursors regulates cancellous bone volume and microarchitecture. |
| doi_str_mv | 10.1016/j.bone.2014.01.023 |
| format | Article |
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Notch1 and Notch2 inactivation in osteoblasts and osteocytes increases cancellous bone volume, but the function of Notch signaling in osteoblast precursors is unknown. To inactivate Notch signaling in immature osteoblastic cells, mice homozygous for conditional Notch1 and Notch2 alleles ( Notch1loxP/loxP ;Notch2loxP/loxP ) were crossed with mice where the osterix ( Osx ) promoter, regulated by a Tet-Off cassette, governs Cre expression ( Osx-Cre ). Notch1loxP/loxP ;Notch2loxP/loxP control and Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ experimental littermate cohorts were obtained. To prevent the effects of embryonic Osx-Cre expression, doxycycline was administered to pregnant dams, but not to newborns. Recombination of conditional alleles was documented in calvarial DNA extracts from 1 month old mice. Notch1 and Notch2 inactivation did not affect femoral microarchitecture at 1 month of age. Cancellous bone volume was higher and structure model index was lower in 3 and 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ mice than in control littermates and the effect was more pronounced in female mice. One month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ male mice transiently exhibited an increase in osteoblast number and a modest suppression in bone resorption. Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice displayed a tendency toward increased bone formation at 3 months of age, although bone remodeling was suppressed in 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice. Notch1 and Notch2 inactivation increased porosity and reduced thickness of cortical bone. These effects were modest and more evident in 3 and 6 month old female than in male mice of the same age. In conclusion, Notch1 and Notch2 expression in osteoblast precursors regulates cancellous bone volume and microarchitecture.</description><identifier>ISSN: 8756-3282</identifier><identifier>EISSN: 1873-2763</identifier><identifier>DOI: 10.1016/j.bone.2014.01.023</identifier><identifier>PMID: 24508387</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Body Weight ; Cortical bone ; Female ; Femur - anatomy & histology ; Femur - diagnostic imaging ; Femur - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Silencing ; Male ; Mice, Inbred C57BL ; Notch1 ; Notch2 ; Organ Size ; Orthopedics ; Osteoblasts ; Osteoblasts - metabolism ; Porosity ; Receptors, Notch - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; X-Ray Microtomography</subject><ispartof>Bone (New York, N.Y.), 2014-05, Vol.62, p.22-28</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><rights>2014 Elsevier Inc. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-eba52e7e063c6e0ac6344bb5a1cc9fdd1911de0dae57ef47af8833d4b9d27aee3</citedby><cites>FETCH-LOGICAL-c573t-eba52e7e063c6e0ac6344bb5a1cc9fdd1911de0dae57ef47af8833d4b9d27aee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bone.2014.01.023$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28340411$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24508387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zanotti, Stefano</creatorcontrib><creatorcontrib>Canalis, Ernesto</creatorcontrib><title>Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture</title><title>Bone (New York, N.Y.)</title><addtitle>Bone</addtitle><description>Abstract Notch receptors regulate cell differentiation and function. Notch1 and Notch2 inactivation in osteoblasts and osteocytes increases cancellous bone volume, but the function of Notch signaling in osteoblast precursors is unknown. To inactivate Notch signaling in immature osteoblastic cells, mice homozygous for conditional Notch1 and Notch2 alleles ( Notch1loxP/loxP ;Notch2loxP/loxP ) were crossed with mice where the osterix ( Osx ) promoter, regulated by a Tet-Off cassette, governs Cre expression ( Osx-Cre ). Notch1loxP/loxP ;Notch2loxP/loxP control and Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ experimental littermate cohorts were obtained. To prevent the effects of embryonic Osx-Cre expression, doxycycline was administered to pregnant dams, but not to newborns. Recombination of conditional alleles was documented in calvarial DNA extracts from 1 month old mice. Notch1 and Notch2 inactivation did not affect femoral microarchitecture at 1 month of age. Cancellous bone volume was higher and structure model index was lower in 3 and 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ mice than in control littermates and the effect was more pronounced in female mice. One month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ male mice transiently exhibited an increase in osteoblast number and a modest suppression in bone resorption. Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice displayed a tendency toward increased bone formation at 3 months of age, although bone remodeling was suppressed in 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice. Notch1 and Notch2 inactivation increased porosity and reduced thickness of cortical bone. These effects were modest and more evident in 3 and 6 month old female than in male mice of the same age. In conclusion, Notch1 and Notch2 expression in osteoblast precursors regulates cancellous bone volume and microarchitecture.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Cortical bone</subject><subject>Female</subject><subject>Femur - anatomy & histology</subject><subject>Femur - diagnostic imaging</subject><subject>Femur - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Silencing</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Notch1</subject><subject>Notch2</subject><subject>Organ Size</subject><subject>Orthopedics</subject><subject>Osteoblasts</subject><subject>Osteoblasts - metabolism</subject><subject>Porosity</subject><subject>Receptors, Notch - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>X-Ray Microtomography</subject><issn>8756-3282</issn><issn>1873-2763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kktv1DAUhS0EokPhD7BA3rBM8CuxR0KVUEULUkUXLQtWlmPfdDxk7JHtVPTf43RKeSxY2fI9597rTweh15S0lND-3bYdYoCWESpaQlvC-BO0okryhsmeP0UrJbu-4UyxI_Qi5y0hhK8lfY6OmOiI4kqu0LcvsdgNxSY4fH9lGH7sE-TsY8A-4JgLxGEyueD6bOeUY8o4wc08mQIZj7CLyUx4522KJtmNL2DLnOAlejaaKcOrh_MYfT37eH36qbm4PP98-uGisZ3kpYHBdAwkkJ7bHoixPRdiGDpDrV2PztE1pQ6IM9BJGIU0o1KcOzGsHZMGgB-jk0Pf_TzswFkIpe6j98nvTLrT0Xj9dyX4jb6Jt7qyIJKJ2oAdGtQP5JxgfPRSohfQeqsX0HoBrQnVFXQ1vflz6qPlF9kqePsgMNmaaUwmWJ9_6xQXRFBade8POqiMbj0kna2HYMH5irtoF_3_9zj5x24nH3yd-B3uIG_jnEKlr6nOTBN9tURiSQQVNQ2sU_wnPtK1Vw</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Zanotti, Stefano</creator><creator>Canalis, Ernesto</creator><general>Elsevier Inc</general><general>Elsevier</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>5PM</scope></search><sort><creationdate>20140501</creationdate><title>Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture</title><author>Zanotti, Stefano ; Canalis, Ernesto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-eba52e7e063c6e0ac6344bb5a1cc9fdd1911de0dae57ef47af8833d4b9d27aee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Cortical bone</topic><topic>Female</topic><topic>Femur - anatomy & histology</topic><topic>Femur - diagnostic imaging</topic><topic>Femur - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Silencing</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Notch1</topic><topic>Notch2</topic><topic>Organ Size</topic><topic>Orthopedics</topic><topic>Osteoblasts</topic><topic>Osteoblasts - metabolism</topic><topic>Porosity</topic><topic>Receptors, Notch - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zanotti, Stefano</creatorcontrib><creatorcontrib>Canalis, Ernesto</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>PubMed Central (Full Participant titles)</collection><jtitle>Bone (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zanotti, Stefano</au><au>Canalis, Ernesto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture</atitle><jtitle>Bone (New York, N.Y.)</jtitle><addtitle>Bone</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>62</volume><spage>22</spage><epage>28</epage><pages>22-28</pages><issn>8756-3282</issn><eissn>1873-2763</eissn><abstract>Abstract Notch receptors regulate cell differentiation and function. Notch1 and Notch2 inactivation in osteoblasts and osteocytes increases cancellous bone volume, but the function of Notch signaling in osteoblast precursors is unknown. To inactivate Notch signaling in immature osteoblastic cells, mice homozygous for conditional Notch1 and Notch2 alleles ( Notch1loxP/loxP ;Notch2loxP/loxP ) were crossed with mice where the osterix ( Osx ) promoter, regulated by a Tet-Off cassette, governs Cre expression ( Osx-Cre ). Notch1loxP/loxP ;Notch2loxP/loxP control and Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ experimental littermate cohorts were obtained. To prevent the effects of embryonic Osx-Cre expression, doxycycline was administered to pregnant dams, but not to newborns. Recombination of conditional alleles was documented in calvarial DNA extracts from 1 month old mice. Notch1 and Notch2 inactivation did not affect femoral microarchitecture at 1 month of age. Cancellous bone volume was higher and structure model index was lower in 3 and 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ mice than in control littermates and the effect was more pronounced in female mice. One month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ male mice transiently exhibited an increase in osteoblast number and a modest suppression in bone resorption. Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice displayed a tendency toward increased bone formation at 3 months of age, although bone remodeling was suppressed in 6 month old Osx-Cre+/− ;Notch1Δ/Δ ;Notch2Δ/Δ female mice. Notch1 and Notch2 inactivation increased porosity and reduced thickness of cortical bone. These effects were modest and more evident in 3 and 6 month old female than in male mice of the same age. In conclusion, Notch1 and Notch2 expression in osteoblast precursors regulates cancellous bone volume and microarchitecture.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>24508387</pmid><doi>10.1016/j.bone.2014.01.023</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Body Weight Cortical bone Female Femur - anatomy & histology Femur - diagnostic imaging Femur - metabolism Fundamental and applied biological sciences. Psychology Gene Silencing Male Mice, Inbred C57BL Notch1 Notch2 Organ Size Orthopedics Osteoblasts Osteoblasts - metabolism Porosity Receptors, Notch - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems X-Ray Microtomography |
| title | Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture |
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