Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Brylka, Laura J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeppert, Sina UNSPECIFIED UNSPECIFIED UNSPECIFIED Babler, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Kratz, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Denecke, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Yorgan, Timur A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Etich, Julia UNSPECIFIED orcid.org/0000-0003-3238-6692 UNSPECIFIED Costa, Ivan G. UNSPECIFIED orcid.org/0000-0003-2890-8697 UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED Boor, Peter UNSPECIFIED orcid.org/0000-0001-9921-4284 UNSPECIFIED Schinke, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Jahnen-Dechent, Willi UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language CAPITAL FEMORAL EPIPHYSIS; CALCIPROTEIN PARTICLES; GLYCOPROTEIN/FETUIN-A; APATITE FORMATION; GENE-EXPRESSION; HS-GLYCOPROTEIN; CELL SUBSETS; GROWTH-PLATE; BONE; CALCIFICATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21383