Brylka, Laura J., Koeppert, Sina, Babler, Anne, Kratz, Beate, Denecke, Bernd, Yorgan, Timur A., Etich, Julia ORCID: 0000-0003-3238-6692, Costa, Ivan G. ORCID: 0000-0003-2890-8697, Brachvogel, Bent, Boor, Peter ORCID: 0000-0001-9921-4284, Schinke, Thorsten and Jahnen-Dechent, Willi (2017). Post-weaning epiphysiolysis causes distal femur dysplasia and foreshortened hindlimbs in fetuin-A-deficient mice. PLoS One, 12 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Fetuin-A / alpha(2)-Heremans-Schmid-glycoprotein (gene name Ahsg) is a systemic inhibitor of ectopic calcification. Due to its high affinity for calcium phosphate, fetuin-A is highly abundant in mineralized bone matrix. Foreshortened femora in fetuin-A-deficient Ahsg(-/-) mice indicated a role for fetuin-A in bone formation. We studied early postnatal bone development in fetuin-A-deficient mice and discovered that femora from Ahsg(-/-) mice exhibited severely displaced distal epiphyses and deformed growth plates, similar to the human disease slipped capital femoral epiphysis (SCFE). The growth plate slippage occurred in 70% of Ahsg(-/-) mice of both sexes around three weeks postnatal. At this time point, mice weaned and rapidly gained weight and mobility. Epiphysis slippage never occurred in wildtype and heterozygous Ahsg(+/-) mice. Homozygous fetuin-A-deficient Ahsg(-/-) mice and, to a lesser degree, heterozygous Ahsg(+/-) mice showed lesions separating the proliferative zone from the hypertrophic zone of the growth plate. The hypertrophic growth plate cartilage in long bones from Ahsg(-/-) mice was significantly elongated and V-shaped until three weeks of age and thus prior to the slippage. Genome-wide transcriptome analysis of laser-dissected distal femoral growth plates from 13-day-old Ahsg(-/-) mice revealed a JAK-STAT-mediated inflammatory response including a 550-fold induction of the chemokine Cxcl9. At this stage, vascularization of the elongated growth plates was impaired, which was visualized by immunofluorescence staining. Thus, fetuin-A-deficient mice may serve as a rodent model of growth plate pathologies including SCFE and inflammatory cartilage degradation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brylka, Laura J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeppert, SinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Babler, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kratz, BeateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denecke, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yorgan, Timur A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Etich, JuliaUNSPECIFIEDorcid.org/0000-0003-3238-6692UNSPECIFIED
Costa, Ivan G.UNSPECIFIEDorcid.org/0000-0003-2890-8697UNSPECIFIED
Brachvogel, BentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boor, PeterUNSPECIFIEDorcid.org/0000-0001-9921-4284UNSPECIFIED
Schinke, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jahnen-Dechent, WilliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-213838
DOI: 10.1371/journal.pone.0187030
Journal or Publication Title: PLoS One
Volume: 12
Number: 10
Date: 2017
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CAPITAL FEMORAL EPIPHYSIS; CALCIPROTEIN PARTICLES; GLYCOPROTEIN/FETUIN-A; APATITE FORMATION; GENE-EXPRESSION; HS-GLYCOPROTEIN; CELL SUBSETS; GROWTH-PLATE; BONE; CALCIFICATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21383

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