Altered endochondral ossification in collagen X mouse models leads to impaired immune responses

Authors

  • E. Sweeney,

    1. Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania
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  • M. Campbell,

    1. Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania
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  • K. Watkins,

    1. Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania
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  • C.A. Hunter,

    1. Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania
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  • O. Jacenko

    Corresponding author
    1. Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania
    • Department of Animal Biology, Division of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Rosenthal Rm 152, Philadelphia, PA 19104-6046
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  • This manuscript is dedicated to the memory of Dr. Elizabeth Dexter Hay, a friend, colleague, and mentor.

Abstract

Disruption of collagen X function in hypertrophic cartilage undergoing endochondral ossification was previously linked to altered hematopoiesis in collagen X transgenic (Tg) and null (KO) mice (Jacenko et al., [2002] Am J Pathol 160:2019–2034). Mice displayed altered growth plates, diminished trabecular bone, and marrow hypoplasia with an aberrant lymphocyte profile throughout life. This study identifies altered B220+, CD4+, and CD8+ lymphocyte numbers, as well as CD4+/fox3P+ T regulatory cells in the collagen X mice. Additionally, diminished in vitro splenocyte responses to mitogens and an inability of mice to survive a challenge with Toxoplasma gondii, confirm impaired immune responses. In concert, ELISA and protein arrays identify aberrant levels of inflammatory, chemo-attractant, and matrix binding cytokines in collagen X mouse sera. These data link the disruption of collagen X function in the chondro-osseous junction to an altered hematopoietic stem cell niche in the marrow, resulting in impaired immune function. Developmental Dynamics 237:2693–2704, 2008. © 2008 Wiley-Liss, Inc.

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