All collagen X Tg and KO mice have skeleto-hematopoietic defects that directly arise from collagen X disruption in hypertrophic cartilage.

<p>Disruption of collagen X function in hypertrophic cartilage of the growth plate results in the loss of a collagen X-containing pericellular network, leading to a reduction and altered compartmentalization of heparan sulfate proteoglycans (HSPGs) within the chondro-osseous junction (COJ) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone.0009518-Jacenko6" target="_blank">[11]</a>, as well as altered cytokine production by COJ cells (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone.0009518-Sweeney1" target="_blank">[8]</a> and unpublished data). Resultant skeletal defects involve all EO-derived skeletal elements, and manifest as compressed growth plates <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone.0009518-Jacenko2" target="_blank">[5]</a>, and reduction in the connectivity, mineral volume and overall amount of trabecular bone (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone-0009518-g001" target="_blank"><b>Fig. 1</b></a> and unpublished data). Collectively, these changes culminate in an altered COJ, which affects the differentiation of resident hematopoietic stem cells, thereby negatively effecting lymphopoiesis and immunity. Hematopoietic defects manifest as impaired lymphopoiesis in the marrow (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone-0009518-g002" target="_blank"><b>Fig. 2</b></a>), with subtle effects on other blood cell lineages (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone-0009518-g005" target="_blank"><b>Fig. 5</b></a>). Secondary hematopoietic/immune defects, arising as a consequence of an altered marrow environment, involve an impaired lymphocyte population in all lymphatic organs (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone-0009518-g003" target="_blank"><b>Figs. 3</b></a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone-0009518-g004" target="_blank"><b>4</b></a>), and impaired immune response throughout life <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009518#pone.0009518-Sweeney1" target="_blank">[8]</a>.