膜联蛋白
矿化(土壤科学)
小泡
造血
内分泌学
化学
膜联蛋白A2
内科学
细胞生物学
医学
生物
生物化学
细胞凋亡
膜
干细胞
有机化学
氮气
作者
Ivan Grskovic,Anna Kutsch,Christian Frie,Gergely Groma,Jacek Stermann,Ursula Schlötzer‐Schrehardt,Anja Niehoff,Stephen E. Moss,Sabrina Rosenbaum,Ernst Pöschl,Markus Chmielewski,Gunter Rappl,Hinrich Abken,John F. Bateman,Kathryn S.E. Cheah,Mats Paulsson,Bent Brachvogel
摘要
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. © 2012 American Society for Bone and Mineral Research.
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