Lan Yu, Tan Xiao-Hong, Weng Tu-Jun, Liu Bing, Yang Xiao
Department of Development and Genetics, Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Feb;16(1):159-63.
It was recently discovered that a subset of osteoblasts functions as a key component of the hematopoietic stem cells (HSC) niche in vivo, controlling HSC self-renewal and multi-lineage differentiation. Disruption of Smad4 gene specifically in osteoblasts leads to a remarkable decrease of osteoblast number and endosteal surface area. In order to elucidate if the osteoblast loss has any effect on hematopoietic activity, the bone marrow (BM) and extramedullary hematopoiesis in the osteoblast-specific Smad4 knockout mice were systematically analyzed, the proportions of mature hematocytes in BM, liver and spleen were detected by flow cytometry, the hematopoietic progenitor number in different stages was measured by colong-forming assay, CFU-S and analysis of LSK cells. The results indicated that the conditional mutant mice demonstrated normal BM hematopoiesis without sign of extramedullary hematopoiesis. Furthermore, the proportion of hematopoietic progenitor cells was normal, while cell number/body weight of the conditional knockout mice increased. It is concluded that hematopoiesis is normally maintained in osteoblast-specific Smad4 knockout mice, and osteoblast loss does not of necessity result in the decrease in BM hematopoiesis.
最近发现，成骨细胞的一个亚群在体内作为造血干细胞（HSC）微环境的关键组成部分，控制着HSC的自我更新和多谱系分化。成骨细胞中Smad4基因的特异性破坏导致成骨细胞数量和骨内膜表面积显著减少。为了阐明成骨细胞缺失是否对造血活性有任何影响，对成骨细胞特异性Smad4基因敲除小鼠的骨髓（BM）和髓外造血进行了系统分析，通过流式细胞术检测BM、肝脏和脾脏中成熟血细胞的比例，通过集落形成试验、CFU-S和LSK细胞分析测量不同阶段的造血祖细胞数量。结果表明，条件性突变小鼠表现出正常的BM造血，没有髓外造血的迹象。此外，造血祖细胞的比例正常，而条件性敲除小鼠的细胞数量/体重增加。结论是，成骨细胞特异性Smad4基因敲除小鼠的造血功能正常维持，成骨细胞缺失不一定导致BM造血减少。
