Altered matrix at the chondro-osseous junction leads to defects in lymphopoiesis.

The collagen X transgenic and null (ColX-Tg/KO) mice have revealed a link between endochondral ossification (EO) and hematopoiesis, and thus serve as model systems to study hematopoietic niches. The altered collagen X function in ColX-Tg/KO mice resulted not only in skeletal defects, which included changes in growth plate ultrastructure, altered localization of heparan sulfate proteoglycans (HSPG), and reduced trabecular bone, but also in hematopoietic defects, which included reduced B lymphocyte numbers throughout life without associated increases in B cell apoptosis. Consequently, the ColX-Tg/KO mice exhibited diminished in vitro and in vivo immune responses. Moreover, reduced expression of several hematopoietic and B lymphopoietic cytokines were measured from ColX-KO-derived hypertrophic chondrocyte and trabecular osteoblast cultures. Together, these data expand the current hematopoietic niche model by including the EO-derived extracellular matrix, for example, the collagen X/HSPG network, as well as the EO-derived hypertrophic chondrocytes and trabecular osteoblasts as hematopoietic signal mediating cells.