Changes in Bone Microarchitecture and Biomechanical Properties in the th3 Thalassemia Mouse are Associated with Decreased Bone Turnover and Occur During the Period of Bone Accrual
Osteoporosis and fractures occur frequently in patients with β-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the β chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse...
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creator | Vogiatzi, Maria G. Tsay, Jaime Verdelis, Kostas Rivella, Stefano Grady, Robert W. Doty, Stephen Giardina, Patricia J. Boskey, Adele L. |
description | Osteoporosis and fractures occur frequently in patients with β-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the β chain of hemoglobin. In this study, we determined the bone abnormalities of the
th3
thalassemia mouse, generated by deletion of the mouse β-chain genes. The heterozygous
th3/+
mouse has moderate anemia and serves as a model of β-thalassemia intermedia, which represents the mild thalassemia phenotype. The
th3/th3
mouse has lethal anemia and is a model of β-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) μCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both
th3/+
and
th3/th3
(
P
|
doi_str_mv | 10.1007/s00223-010-9365-0 |
format | Article |
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th3
thalassemia mouse, generated by deletion of the mouse β-chain genes. The heterozygous
th3/+
mouse has moderate anemia and serves as a model of β-thalassemia intermedia, which represents the mild thalassemia phenotype. The
th3/th3
mouse has lethal anemia and is a model of β-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) μCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both
th3/+
and
th3/th3
(
P
< 0.05); (2) cortical bone analysis showed thinner cortices and increased marrow area in
th3/+
(
P
< 0.05); (3) μCT abnormalities in
th3/+
mice were present by 2 months and did not worsen with age; (4) histomorphometry was significant for decreased bone formation and resorption in both
th3/+
and
th3/th3
, and expression of cathepsin K and osteocalcin from bone of both
th3/+
and
th3/th3
animals was reduced (
P
< 0.05); (5) biomechanics showed reduced maximum load, maximum moment, and structural stiffness in both
th3/+
and
th3/th3
(
P
< 0.01). In conclusion, the
th3
mouse model of thalassemia manifests bone changes reminiscent of those in humans and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover and develop early during the period of bone accrual.</description><identifier>ISSN: 0171-967X</identifier><identifier>EISSN: 1432-0827</identifier><identifier>DOI: 10.1007/s00223-010-9365-0</identifier><identifier>PMID: 20449578</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Animals ; Biochemistry ; Biomechanical Phenomena ; Biomechanics ; Biomedical and Life Sciences ; Blood diseases ; Bone and Bones ; Bone density ; Bone diseases ; Bone Remodeling - physiology ; Cell Biology ; Endocrinology ; Erythropoiesis ; Life Sciences ; Mice ; Mice, Inbred C57BL ; Orthopedics ; Osteoporosis - etiology ; Osteoporosis - pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Spectroscopy, Fourier Transform Infrared ; Thalassemia - complications ; Thalassemia - genetics ; Tomography, X-Ray Computed</subject><ispartof>Calcified tissue international, 2010-06, Vol.86 (6), p.484-494</ispartof><rights>Springer Science+Business Media, LLC 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-cba129a9e8de84e3c365954c706a3ffe811879d49cadf6dc08dbb45f706fccf13</citedby><cites>FETCH-LOGICAL-c445t-cba129a9e8de84e3c365954c706a3ffe811879d49cadf6dc08dbb45f706fccf13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00223-010-9365-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00223-010-9365-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27931,27932,41495,42564,51326</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20449578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vogiatzi, Maria G.</creatorcontrib><creatorcontrib>Tsay, Jaime</creatorcontrib><creatorcontrib>Verdelis, Kostas</creatorcontrib><creatorcontrib>Rivella, Stefano</creatorcontrib><creatorcontrib>Grady, Robert W.</creatorcontrib><creatorcontrib>Doty, Stephen</creatorcontrib><creatorcontrib>Giardina, Patricia J.</creatorcontrib><creatorcontrib>Boskey, Adele L.</creatorcontrib><title>Changes in Bone Microarchitecture and Biomechanical Properties in the th3 Thalassemia Mouse are Associated with Decreased Bone Turnover and Occur During the Period of Bone Accrual</title><title>Calcified tissue international</title><addtitle>Calcif Tissue Int</addtitle><addtitle>Calcif Tissue Int</addtitle><description>Osteoporosis and fractures occur frequently in patients with β-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the β chain of hemoglobin. In this study, we determined the bone abnormalities of the
th3
thalassemia mouse, generated by deletion of the mouse β-chain genes. The heterozygous
th3/+
mouse has moderate anemia and serves as a model of β-thalassemia intermedia, which represents the mild thalassemia phenotype. The
th3/th3
mouse has lethal anemia and is a model of β-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) μCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both
th3/+
and
th3/th3
(
P
< 0.05); (2) cortical bone analysis showed thinner cortices and increased marrow area in
th3/+
(
P
< 0.05); (3) μCT abnormalities in
th3/+
mice were present by 2 months and did not worsen with age; (4) histomorphometry was significant for decreased bone formation and resorption in both
th3/+
and
th3/th3
, and expression of cathepsin K and osteocalcin from bone of both
th3/+
and
th3/th3
animals was reduced (
P
< 0.05); (5) biomechanics showed reduced maximum load, maximum moment, and structural stiffness in both
th3/+
and
th3/th3
(
P
< 0.01). In conclusion, the
th3
mouse model of thalassemia manifests bone changes reminiscent of those in humans and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover and develop early during the period of bone accrual.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomechanical Phenomena</subject><subject>Biomechanics</subject><subject>Biomedical and Life Sciences</subject><subject>Blood diseases</subject><subject>Bone and Bones</subject><subject>Bone density</subject><subject>Bone diseases</subject><subject>Bone Remodeling - physiology</subject><subject>Cell Biology</subject><subject>Endocrinology</subject><subject>Erythropoiesis</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Orthopedics</subject><subject>Osteoporosis - etiology</subject><subject>Osteoporosis - pathology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><subject>Thalassemia - complications</subject><subject>Thalassemia - genetics</subject><subject>Tomography, X-Ray Computed</subject><issn>0171-967X</issn><issn>1432-0827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkUtv1DAUhSMEokPhB7BBFhtWgetHHl5Op-UhtWoXg8TO8tzcNK6SeLATEL-rfxDPpICEhFhYluXvnKN7T5a95PCWA1TvIoAQMgcOuZZlkcOjbMWVFDnUonqcrYBXPNdl9eUkexbjHQBXZVk-zU4EKKWLql5l95vOjrcUmRvZmR-JXTkM3gbs3EQ4zYGYHRt25vxAmFCHtmc3we8pTG6RTR2lI9m2s72NkQZn2ZWfY1Im9TpGj85O1LDvburYOWEgG9PzGLedw-i_UTimXCPOgZ3PwY23R9sbCs43zLcLvEYMs-2fZ09a20d68XCfZp_fX2w3H_PL6w-fNuvLHJUqphx3lgttNdUN1YokphXpQmEFpZVtSzXndaUbpdE2bdkg1M1up4o2_beILZen2ZvFdx_815niZAYXkfrejpTmM5UqhagLof9PSlkUCuSBfP0XeefTCtIYRoLSUIKqE8QXKFURY6DW7IMbbPhhOJhD82Zp3qTmzaF5A0nz6sF43g3U_Fb8qjoBYgHi_rBfCn-S_-36E2Lwuyc</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Vogiatzi, Maria G.</creator><creator>Tsay, Jaime</creator><creator>Verdelis, Kostas</creator><creator>Rivella, Stefano</creator><creator>Grady, Robert W.</creator><creator>Doty, Stephen</creator><creator>Giardina, Patricia J.</creator><creator>Boskey, Adele L.</creator><general>Springer-Verlag</general><general>Springer Nature 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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20100601</creationdate><title>Changes in Bone Microarchitecture and Biomechanical Properties in the th3 Thalassemia Mouse are Associated with Decreased Bone Turnover and Occur During the Period of Bone Accrual</title><author>Vogiatzi, Maria G. ; Tsay, Jaime ; Verdelis, Kostas ; Rivella, Stefano ; Grady, Robert W. ; Doty, Stephen ; Giardina, Patricia J. ; Boskey, Adele L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-cba129a9e8de84e3c365954c706a3ffe811879d49cadf6dc08dbb45f706fccf13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Biomechanical Phenomena</topic><topic>Biomechanics</topic><topic>Biomedical and Life Sciences</topic><topic>Blood diseases</topic><topic>Bone and Bones</topic><topic>Bone density</topic><topic>Bone diseases</topic><topic>Bone Remodeling - physiology</topic><topic>Cell Biology</topic><topic>Endocrinology</topic><topic>Erythropoiesis</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Orthopedics</topic><topic>Osteoporosis - etiology</topic><topic>Osteoporosis - pathology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rodents</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><topic>Thalassemia - complications</topic><topic>Thalassemia - genetics</topic><topic>Tomography, X-Ray Computed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vogiatzi, Maria G.</creatorcontrib><creatorcontrib>Tsay, Jaime</creatorcontrib><creatorcontrib>Verdelis, Kostas</creatorcontrib><creatorcontrib>Rivella, Stefano</creatorcontrib><creatorcontrib>Grady, Robert W.</creatorcontrib><creatorcontrib>Doty, Stephen</creatorcontrib><creatorcontrib>Giardina, Patricia J.</creatorcontrib><creatorcontrib>Boskey, Adele L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Calcified tissue international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vogiatzi, Maria G.</au><au>Tsay, Jaime</au><au>Verdelis, Kostas</au><au>Rivella, Stefano</au><au>Grady, Robert W.</au><au>Doty, Stephen</au><au>Giardina, Patricia J.</au><au>Boskey, Adele L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in Bone Microarchitecture and Biomechanical Properties in the th3 Thalassemia Mouse are Associated with Decreased Bone Turnover and Occur During the Period of Bone Accrual</atitle><jtitle>Calcified tissue international</jtitle><stitle>Calcif Tissue Int</stitle><addtitle>Calcif Tissue Int</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>86</volume><issue>6</issue><spage>484</spage><epage>494</epage><pages>484-494</pages><issn>0171-967X</issn><eissn>1432-0827</eissn><abstract>Osteoporosis and fractures occur frequently in patients with β-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the β chain of hemoglobin. In this study, we determined the bone abnormalities of the
th3
thalassemia mouse, generated by deletion of the mouse β-chain genes. The heterozygous
th3/+
mouse has moderate anemia and serves as a model of β-thalassemia intermedia, which represents the mild thalassemia phenotype. The
th3/th3
mouse has lethal anemia and is a model of β-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) μCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both
th3/+
and
th3/th3
(
P
< 0.05); (2) cortical bone analysis showed thinner cortices and increased marrow area in
th3/+
(
P
< 0.05); (3) μCT abnormalities in
th3/+
mice were present by 2 months and did not worsen with age; (4) histomorphometry was significant for decreased bone formation and resorption in both
th3/+
and
th3/th3
, and expression of cathepsin K and osteocalcin from bone of both
th3/+
and
th3/th3
animals was reduced (
P
< 0.05); (5) biomechanics showed reduced maximum load, maximum moment, and structural stiffness in both
th3/+
and
th3/th3
(
P
< 0.01). In conclusion, the
th3
mouse model of thalassemia manifests bone changes reminiscent of those in humans and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover and develop early during the period of bone accrual.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>20449578</pmid><doi>10.1007/s00223-010-9365-0</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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ispartof | Calcified tissue international, 2010-06, Vol.86 (6), p.484-494 |
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language | eng |
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source | MEDLINE; SpringerNature Journals |
subjects | Animals Biochemistry Biomechanical Phenomena Biomechanics Biomedical and Life Sciences Blood diseases Bone and Bones Bone density Bone diseases Bone Remodeling - physiology Cell Biology Endocrinology Erythropoiesis Life Sciences Mice Mice, Inbred C57BL Orthopedics Osteoporosis - etiology Osteoporosis - pathology Reverse Transcriptase Polymerase Chain Reaction Rodents Spectroscopy, Fourier Transform Infrared Thalassemia - complications Thalassemia - genetics Tomography, X-Ray Computed |
title | Changes in Bone Microarchitecture and Biomechanical Properties in the th3 Thalassemia Mouse are Associated with Decreased Bone Turnover and Occur During the Period of Bone Accrual |
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