Universität zu Köln

Grskovic, Ivan, Kutsch, Anna, Frie, Christian, Groma, Gergely, Stermann, Jacek, Schloetzer-Schrehardt, Ursula, Niehoff, Anja ORCID: 0000-0002-4165-0929, Moss, Stephen E., Rosenbaum, Sabrina, Poeschl, Ernst, Chmielewski, Markus, Rappl, Gunter, Abken, Hinrich, Bateman, John F., Cheah, Kathryn S. E., Paulsson, Mats and Brachvogel, Bent (2012). Depletion of Annexin A5, Annexin A6, and Collagen X Causes No Gross Changes in Matrix Vesicle-Mediated Mineralization, but Lack of Collagen X Affects Hematopoiesis and the Th1/Th2 Response. J. Bone Miner. Res., 27 (11). S. 2399 - 2413. HOBOKEN: WILEY-BLACKWELL. ISSN 0884-0431

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Abstract

Numerous biochemical studies have pointed to an essential role of annexin A5 (AnxA5), annexin A6 (AnxA6), and collagen X in matrix vesicle-mediated biomineralization during endochondral ossification and in osteoarthritis. By binding to the extracellular matrix protein collagen X and matrix vesicles, annexins were proposed to anchor matrix vesicles in the extracellular space of hypertrophic chondrocytes to initiate the calcification of cartilage. However, mineralization appears to be normal in mice lacking AnxA5 and AnxA6, whereas collagen X-deficient mice show only subtle alterations in the growth plate organization. We hypothesized that the simultaneous lack of AnxA5, AnxA6, and collagen X in vivo induces more pronounced changes in the growth plate development and the initiation of mineralization. In this study, we generated and analyzed mice deficient for AnxA5, AnxA6, and collagen X. Surprisingly, mice were viable, fertile, and showed no obvious abnormalities. Assessment of growth plate development indicated that the hypertrophic zone was expanded in Col10a1(-/-) and AnxA5(-/-) AnxA6(-/-) Col10a1(-/-) newborns, whereas endochondral ossification and mineralization were not affected in 13-day- and 1-month-old mutants. In peripheral quantitative computed tomography, no changes in the degree of biomineralization were found in femora of 1-month- and 1-year-old mutants even though the diaphyseal circumference was reduced in Col10a1(-/-) and AnxA5(-/-) AnxA6(-/-) Col10a1(-/-) mice. The percentage of naive immature IgM(+)/IgM(+) B cells and peripheral T-helper cells were increased in Col10a1(-/)- and AnxA5(-/-) AnxA6(-/-) Col10a1(-/-) mutants, and activated splenic T cells isolated from Col10a1(-/-) mice secreted elevated levels of IL-4 and GM-CSF. Hence, collagen X is needed for hematopoiesis during endochondral ossification and for the immune response, but the interaction of annexin A5, annexin A6, and collagen X is not essential for physiological calcification of growth plate cartilage. Therefore, annexins and collagen X may rather fulfill functions in growth plate cartilage not directly linked to the mineralization process. (C) 2012 American Society for Bone and Mineral Research.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grskovic, Ivan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kutsch, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Frie, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Groma, Gergely UNSPECIFIED UNSPECIFIED UNSPECIFIED Stermann, Jacek UNSPECIFIED UNSPECIFIED UNSPECIFIED Schloetzer-Schrehardt, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED orcid.org/0000-0002-4165-0929 UNSPECIFIED Moss, Stephen E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenbaum, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Poeschl, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Rappl, Gunter UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Bateman, John F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cheah, Kathryn S. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480543
DOI:	10.1002/jbmr.1682
Journal or Publication Title:	J. Bone Miner. Res.
Volume:	27
Number:	11
Page Range:	S. 2399 - 2413
Date:	2012
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	0884-0431
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-PLATE CARTILAGE; IN-VITRO; ENDOCHONDRAL OSSIFICATION; OSTEOARTHRITIC CARTILAGE; EXTRACELLULAR-MATRIX; PERIVASCULAR CELLS; II COLLAGEN; NULL MICE; PHOSPHATIDYLSERINE; DIFFERENTIATION Multiple languages Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48054