Defective endochondral ossification-derived matrix and bone cells alter the lymphopoietic niche in collagen X mouse models.
Defective endochondral ossification-derived matrix and bone cells alter the lymphopoietic niche in collagen X mouse models.
复制标题
有缺陷的软骨内骨化衍生基质和骨细胞改变了 X 型胶原小鼠模型中的淋巴细胞生成生态位。
DOI：
10.1089/scd.2012.0387
复制
发表时间：
2013
影响因子：
4
通讯作者：
Jacenko,Olena
中科院分区：
文献类型：
--
作者：
Sweeney,Elizabeth;Roberts,Douglas;Lin,Angela;Guldberg,Robert;Jacenko,Olena
尽管骨骼和造血发育相互依赖，造血生态位的细胞和基质成分仍有待充分界定。利用X型胶原（ColX）（一种与软骨内骨化相关的主要肥大软骨基质蛋白）功能受损的小鼠，我们的数据确定了软骨-骨造血生态位处的小梁骨细胞中的细胞因子缺陷是这些小鼠异常B淋巴细胞生成的原因。具体而言，通过微计算机断层扫描对ColX转基因和无效小鼠软骨-骨区域的分析揭示了改变的骨小梁环境。此外，造血和软骨-骨细胞类型的共培养物突出了ColX转基因和空小鼠来源的小梁骨细胞的造血支持受损。此外，细胞因子阵列与条件培养基从小梁成骨细胞共培养物中提出了一个异常的造血细胞因子环境内的软骨-骨龛的ColX缺陷小鼠。因此，在补充白细胞介素-7、干细胞因子和基质衍生因子-1的ColX小鼠衍生的小梁成骨细胞共培养物中，B淋巴细胞生成被拯救。此外，B细胞发育在注射白细胞介素-7后在体内恢复。这些数据支持我们的假设，endrochondrally-derived小梁骨细胞和基质成分提供了富含精氨酸的造血小生境。此外，这项研究有助于新兴的概念，生态位缺陷可能是某些免疫-骨和造血系统疾病的基础。
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.