剔除成骨细胞特异性基因Smad4不影响小鼠造血稳态的维持

Hematopoiesis Is Normally Maintained in Osteoblast-specific Smad4 Gene Knockout Mice

体内证实,成骨细胞作为造血干细胞(HSC)niche的组成部分是随着基因修饰小鼠模型的建立而实现的,成骨细胞构成了HSC自我更新和多向分化的重要微环境。Smad4基因在成骨细胞的特异性剔除可导致小鼠成骨细胞数量的下降和骨内膜面积的减少。为了阐明体内成骨细胞的减少是否影响小鼠骨髓的造血活性,本研究对成骨细胞特异性Smad4基因剔除小鼠的骨髓和髓外造血进行了系统分析,采用流式细胞技术检测骨髓和肝脏、脾脏成熟血细胞的比例;用集落培养技术、脾结节形成实验和LSK细胞分析检测不同阶段造血前体细胞的数量。结果显示,条件剔除小鼠的骨髓造血稳态维持正常,没有髓外造血的表现,特别是其不同阶段的造血前体细胞比例正常,而单位体重的细胞数量反而增加。结论:体内成骨细胞数量的减少不是导致骨髓造血活性下降的决定性因素。

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 Srnad4 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 hematopoiefic activity, the bone marrow （BM） and extramedullary hematopoiesis in the osteoblast-specific Srnad4 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 Srnad4 knockout mice, and osteoblast loss does not of necessity result in the decrease in BM hematopoiesis.