{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:36:53Z","timestamp":1790105813692,"version":"4.0.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:00:00Z","timestamp":1339459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Numerous biochemical studies have pointed to an essential role of annexin A5 (AnxA5), annexin A6 (AnxA6), and collagen X in matrix vesicle\u2013mediated 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\u2013deficient 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\u2212\/\u2212 and AnxA5\u2212\/\u2212AnxA6\u2212\/\u2212Col10a1\u2212\/\u2212 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\u2212\/\u2212 and AnxA5\u2212\/\u2212AnxA6\u2212\/\u2212Col10a1\u2212\/\u2212 mice. The percentage of naive immature IgM+\/IgM+ B cells and peripheral T-helper cells were increased in Col10a1\u2212\/\u2212 and AnxA5\u2212\/\u2212AnxA6\u2212\/\u2212Col10a1\u2212\/\u2212 mutants, and activated splenic T cells isolated from Col10a1\u2212\/\u2212 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. \u00a9 2012 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.1682","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T16:07:08Z","timestamp":1339517228000},"page":"2399-2412","source":"Crossref","is-referenced-by-count":38,"title":["Depletion of annexin A5, annexin A6, and collagen X causes no gross changes in matrix vesicle\u2013mediated mineralization, but lack of collagen X affects hematopoiesis and the Th1\/Th2 response"],"prefix":"10.1093","volume":"27","author":[{"given":"Ivan","family":"Grskovic","sequence":"first","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kutsch","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Frie","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergely","family":"Groma","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Stermann","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Schl\u00f6tzer-Schrehardt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Niehoff","sequence":"additional","affiliation":[{"name":"Institute of Biomechanics and Orthopaedics, German Sport University Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E","family":"Moss","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Institute of Ophthalmology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"P\u00f6schl","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Chmielewski","sequence":"additional","affiliation":[{"name":"Tumorgenetics, Department I of Internal Medicine, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Rappl","sequence":"additional","affiliation":[{"name":"Tumorgenetics, Department I of Internal Medicine, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinrich","family":"Abken","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany"},{"name":"Tumorgenetics, Department I of Internal Medicine, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Bateman","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute and Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn SE","family":"Cheah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"Paulsson","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany"},{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, 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