Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice
ABSTRACT Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated...
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Veröffentlicht in: | Journal of bone and mineral research 2015-08, Vol.30 (8), p.1468-1480 |
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description | ABSTRACT
Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L5 vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research. |
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Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L5 vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.2488</identifier><identifier>PMID: 25707500</identifier><language>eng</language><publisher>England</publisher><subject>Adaptation, Physiological ; Animals ; Estrogen Receptor alpha - deficiency ; Female ; GENETIC ANIMAL MODEL ; Lumbar Vertebrae - metabolism ; Lumbar Vertebrae - pathology ; Male ; Mice ; Mice, Knockout ; Organ Size ; OSTEOBLASTS ; Osteoblasts - metabolism ; Osteoblasts - pathology ; Osteocalcin - genetics ; Osteocalcin - metabolism ; Osteocytes - metabolism ; OSTEOPOROSIS ; Sex Characteristics ; SEX STEROIDS ; Tibia - metabolism ; Tibia - pathology</subject><ispartof>Journal of bone and mineral research, 2015-08, Vol.30 (8), p.1468-1480</ispartof><rights>2015 American Society for Bone and Mineral Research</rights><rights>2015 American Society for Bone and Mineral Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3788-9cf02f346059fbd24d85cee575be9bece6c7e8583db7555fcf2a783ef84f97943</citedby><cites>FETCH-LOGICAL-c3788-9cf02f346059fbd24d85cee575be9bece6c7e8583db7555fcf2a783ef84f97943</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%2Fjbmr.2488$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.2488$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25707500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Melville, Katherine M</creatorcontrib><creatorcontrib>Kelly, Natalie H</creatorcontrib><creatorcontrib>Surita, Gina</creatorcontrib><creatorcontrib>Buchalter, Daniel B</creatorcontrib><creatorcontrib>Schimenti, John C</creatorcontrib><creatorcontrib>Main, Russell P</creatorcontrib><creatorcontrib>Ross, F Patrick</creatorcontrib><creatorcontrib>van der Meulen, Marjolein CH</creatorcontrib><title>Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT
Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L5 vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.</description><subject>Adaptation, Physiological</subject><subject>Animals</subject><subject>Estrogen Receptor alpha - deficiency</subject><subject>Female</subject><subject>GENETIC ANIMAL MODEL</subject><subject>Lumbar Vertebrae - metabolism</subject><subject>Lumbar Vertebrae - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Organ Size</subject><subject>OSTEOBLASTS</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoblasts - pathology</subject><subject>Osteocalcin - genetics</subject><subject>Osteocalcin - metabolism</subject><subject>Osteocytes - metabolism</subject><subject>OSTEOPOROSIS</subject><subject>Sex Characteristics</subject><subject>SEX STEROIDS</subject><subject>Tibia - metabolism</subject><subject>Tibia - pathology</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1O3DAURq2qVRmmXfQFKi_LIoPj-C9LmBloq4mQULuOHOeaGiX2NM4IsWPNilfhRXgInoRkBtghVvcuzneurj6EvqVklhJCDy-rtptRptQHNEk5zRImVPoRTYhSLCEsS_fQfoyXhBDBhfiM9iiXRHJCJuh2aS2YPuJg8QIa6F3w4748f7jHzuOz2EOoGh37x5u7lfOgLwDPoWmGhMfHwQMudIxY-xof1Xrd662hD7gA8097Z3SDV0HXzl_ghRuOdaP2BFrdwDZVjEvhDHxBn6xuInx9nlP092T5Z_4zWZ2d_pofrRKTSaWS3FhCbcYE4bmtaspqxQ0Al7yCvAIDwkhQXGV1JTnn1liqpcrAKmZzmbNsin7svOsu_N9A7MvWRTO8pD2ETSxTRZQQnKn8fVTkkqaSUT6gBzvUdCHGDmy57lyru-syJeXYUjm2VI4tDez3Z-2maqF-JV9qGYDDHXDlGrh-21T-Pi7Ot8onTCmduw</recordid><startdate>201508</startdate><enddate>201508</enddate><creator>Melville, Katherine M</creator><creator>Kelly, Natalie H</creator><creator>Surita, Gina</creator><creator>Buchalter, Daniel B</creator><creator>Schimenti, John C</creator><creator>Main, Russell P</creator><creator>Ross, F Patrick</creator><creator>van der Meulen, Marjolein CH</creator><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>201508</creationdate><title>Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice</title><author>Melville, Katherine M ; Kelly, Natalie H ; Surita, Gina ; Buchalter, Daniel B ; Schimenti, John C ; Main, Russell P ; Ross, F Patrick ; van der Meulen, Marjolein CH</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3788-9cf02f346059fbd24d85cee575be9bece6c7e8583db7555fcf2a783ef84f97943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adaptation, Physiological</topic><topic>Animals</topic><topic>Estrogen Receptor alpha - deficiency</topic><topic>Female</topic><topic>GENETIC ANIMAL MODEL</topic><topic>Lumbar Vertebrae - metabolism</topic><topic>Lumbar Vertebrae - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Organ Size</topic><topic>OSTEOBLASTS</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoblasts - pathology</topic><topic>Osteocalcin - genetics</topic><topic>Osteocalcin - metabolism</topic><topic>Osteocytes - metabolism</topic><topic>OSTEOPOROSIS</topic><topic>Sex Characteristics</topic><topic>SEX STEROIDS</topic><topic>Tibia - metabolism</topic><topic>Tibia - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Melville, Katherine M</creatorcontrib><creatorcontrib>Kelly, Natalie H</creatorcontrib><creatorcontrib>Surita, Gina</creatorcontrib><creatorcontrib>Buchalter, Daniel B</creatorcontrib><creatorcontrib>Schimenti, John C</creatorcontrib><creatorcontrib>Main, Russell P</creatorcontrib><creatorcontrib>Ross, F Patrick</creatorcontrib><creatorcontrib>van der Meulen, Marjolein CH</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>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Melville, Katherine M</au><au>Kelly, Natalie H</au><au>Surita, Gina</au><au>Buchalter, Daniel B</au><au>Schimenti, John C</au><au>Main, Russell P</au><au>Ross, F Patrick</au><au>van der Meulen, Marjolein CH</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2015-08</date><risdate>2015</risdate><volume>30</volume><issue>8</issue><spage>1468</spage><epage>1480</epage><pages>1468-1480</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><abstract>ABSTRACT
Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed‐background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell–specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin‐Cre (OC‐Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC‐ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro‐CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC‐ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC‐ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC‐ERαKO female L5 vertebrae and with increased maximum moment in pOC‐ERαKO male femora. Female pOC‐ERαKO mice responded more to mechanical loading, whereas the response of pOC‐ERαKO male animals was similar to their littermate controls. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.</abstract><cop>England</cop><pmid>25707500</pmid><doi>10.1002/jbmr.2488</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptation, Physiological Animals Estrogen Receptor alpha - deficiency Female GENETIC ANIMAL MODEL Lumbar Vertebrae - metabolism Lumbar Vertebrae - pathology Male Mice Mice, Knockout Organ Size OSTEOBLASTS Osteoblasts - metabolism Osteoblasts - pathology Osteocalcin - genetics Osteocalcin - metabolism Osteocytes - metabolism OSTEOPOROSIS Sex Characteristics SEX STEROIDS Tibia - metabolism Tibia - pathology |
title | Effects of Deletion of ERα in Osteoblast‐Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice |
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