Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

Hdl Handle:
http://hdl.handle.net/10675.2/834
Title:
Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice
Authors:
Seto, Jong; Busse, Bjorn; Gupta, Himadri S.; Schafer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; Catala-Lehnen, Philip; Schinke, Thorsten; Fratzl, Peter ( 0000-0003-4437-7830 ) ; Jahnen-Dechent, Willi ( 0000-0003-1315-4407 )
Abstract:
The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.
Editors:
Isales, Carlos M.
Citation:
PLoS One. 2012 Oct 16; 7(10):e47338
Issue Date:
16-Oct-2012
URI:
http://hdl.handle.net/10675.2/834
DOI:
10.1371/journal.pone.0047338
PubMed ID:
23091616
PubMed Central ID:
PMC3473050
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Medicine Faculty: Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorSeto, Jong-
dc.contributor.authorBusse, Bjorn-
dc.contributor.authorGupta, Himadri S.-
dc.contributor.authorSchafer, Cora-
dc.contributor.authorKrauss, Stefanie-
dc.contributor.authorDunlop, John W. C.-
dc.contributor.authorMasic, Admir-
dc.contributor.authorKerschnitzki, Michael-
dc.contributor.authorZaslansky, Paul-
dc.contributor.authorBoesecke, Peter-
dc.contributor.authorCatala-Lehnen, Philip-
dc.contributor.authorSchinke, Thorsten-
dc.contributor.authorFratzl, Peter-
dc.contributor.authorJahnen-Dechent, Willi-
dc.contributor.editorIsales, Carlos M.-
dc.date.accessioned2012-10-26T20:35:14Z-
dc.date.available2012-10-26T20:35:14Z-
dc.date.issued2012-10-16en_US
dc.identifier.citationPLoS One. 2012 Oct 16; 7(10):e47338en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid23091616en_US
dc.identifier.doi10.1371/journal.pone.0047338en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/834-
dc.description.abstractThe plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectExtracellular Matrixen_US
dc.subjectConnective Tissueen_US
dc.subjectMaterials Scienceen_US
dc.subjectBiomaterialsen_US
dc.subjectMaterial Propertiesen_US
dc.subjectMechanical Propertiesen_US
dc.subjectNatural Materialsen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMusculoskeletal Systemen_US
dc.subjectBoneen_US
dc.subjectCartilageen_US
dc.subjectComparative Anatomyen_US
dc.titleAccelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Miceen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3473050en_US
dc.contributor.corporatenameDepartment of Medicine-
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomy-
dc.contributor.corporatenameCollege of Graduate Studies-
dc.contributor.corporatenameDepartment of Orthopaedic Surgery-

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