title: Defective endochondral ossification-derived matrix and bone cells alter the lymphopoietic niche in collagen X mouse models.
abstract: Despite the appreciated interdependence of skeletal and hematopoietic development, the cell and matrix components of the hematopoietic niche remain to be fully defined. Utilizing mice with disrupted function of collagen X (ColX), a major hypertrophic cartilage matrix protein associated with endochondral ossification, our data identified a cytokine defect in trabecular bone cells at the chondro-osseous hematopoietic niche as a cause for aberrant B lymphopoiesis in these mice. Specifically, analysis of ColX transgenic and null mouse chondro-osseous regions via micro-computed tomography revealed an altered trabecular bone environment. Additionally, cocultures with hematopoietic and chondro-osseous cell types highlighted impaired hematopoietic support by ColX transgenic and null mouse derived trabecular bone cells. Further, cytokine arrays with conditioned media from the trabecular osteoblast cocultures suggested an aberrant hematopoietic cytokine milieu within the chondro-osseous niche of the ColX deficient mice. Accordingly, B lymphopoiesis was rescued in the ColX mouse derived trabecular osteoblast cocultures with interlukin-7, stem cell factor, and stromal derived factor-1 supplementation. Moreover, B cell development was restored in vivo after injections of interlukin-7. These data support our hypothesis that endrochondrally-derived trabecular bone cells and matrix constituents provide cytokine-rich niches for hematopoiesis. Furthermore, this study contributes to the emerging concept that niche defects may underlie certain immuno-osseous and hematopoietic disorders.
authors: 1 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors: Elizabeth
authors: E
authors: Sweeney
authors: Douglas
authors: D
authors: Roberts
authors: Angela
authors: A
authors: Lin
authors: Robert
authors: R
authors: Guldberg
authors: Olena
authors: O
authors: Jacenko
mesh_terms: D016475:3T3 Cells; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology; D002478:Cells, Cultured; D024121:Collagen Type X / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D019707:Receptors, Chemokine / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D024121:Collagen Type X; C503133:Gr-1 protein, mouse; D019812:Heparan Sulfate Proteoglycans; D015851:Interleukin-7; D019707:Receptors, Chemokine; D019089:Stem Cell Factor
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