Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment
Acute hematopoietic stress in mice is followed by enhanced osteoclast maturation in the bone marrow microenvironment
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DOI：
10.1016/j.exphem.2014.07.262
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发表时间：
2014-11-01
影响因子：
2.6
通讯作者：
Katavic, Vedran
中科院分区：
文献类型：
--
作者：
Kuzmac, Sonia;Grcevic, Danka;Katavic, Vedran
破骨细胞是造血干细胞（HSC）生态位的组成部分，但它们在造血干细胞稳态和释放中的作用仍存在争议。我们的目的是研究急性失血量达到总血含量的10%，并随之产生强烈的造血功能，是否会影响破骨细胞的分化和活性。研究了从后肢骨骼中分离的外周血、脾脏和骨髓（BM）细胞中是否存在特定的破骨细胞前体亚群：BM中存在B220(-)CD3(-)NK1.1(-) CD11(-/low)CD115(+)CD117（+）细胞，外周血和脾脏中存在B220(-)CD3(-)NK1.1(-)Gr-1(-)CD11b(+)CD115（+）细胞，以及核因子κ b - b +周期停止的静态破骨细胞前体的受体激活剂。我们还评估了破骨细胞发生相关基因CD115、核因子κ b受体激活因子和组织蛋白酶K的表达，以及BM细胞在体外形成破骨细胞样细胞的潜力和体内破骨细胞活性。我们观察到，在失血后的第1周，脾脏细胞数量和骨髓生成增加，对骨髓细胞或骨髓前体细胞（包括具有高破骨潜能的细胞）没有任何显著影响。然而，在出血后1周，造血功能显著促进组织蛋白酶K、白细胞介素-34和骨形态发生蛋白-6的表达。脾脏中静态破骨细胞前体在出血后2天显著增加，而破骨细胞活性在出血后2周保持不变。破骨细胞依赖的b细胞分化在BM的前b成熟阶段受到影响，而Lin(-)Sca-1(+)c-kit（+）群体在出血后2天后在BM和脾脏中扩增。我们的数据表明，急性失血在出血后1周促进破骨细胞的分化和成熟，但在出血后2周不增强骨吸收。我们的数据还确定破骨细胞分化是造血应激后建立HSC稳态的后续和重要事件。(C) 2014 ISEH -国际实验血液学学会。Elsevier Inc.出版。
Osteoclasts are components of hematopoietic stem cell (HSC) niches, but their role as contributors to the HSC homeostasis and release are still controversial. We aimed to investigate whether an acute blood loss of 10% of total blood content, along with the consequent intense hematopoiesis, would affect osteoclast differentiation and activity. Isolated peripheral blood, spleen, and bone marrow (BM) cells from bones of hind limbs were investigated for the presence of specific subpopulations of osteoclast precursors: B220(-)CD3(-)NK1.1(-) CD11(-/low)CD115(+)CD117(+) cells in BM, and B220(-)CD3(-)NK1.1(-)Gr-1(-)CD11b(+)CD115(+) cells in peripheral blood and spleen as well as the receptor activator of nuclear factor kappa-B+ cycle-arrested quiescent osteoclast precursors. Expression of osteoclastogenesis-related genes CD115, receptor activator of nuclear factor kappa-B, and cathepsin K, the potential of BM cells to form osteoclast-like cells in vitro, and osteoclast activity in vivo were also evaluated. We observed an increase in spleen cellularity and myelopoiesis during week 1 following blood loss, without any significant effects on BM cellularity or BM myeloid precursors, including cells with high osteoclastogenic potential. However, at 1 week postbleeding, hematopoiesis significantly promoted the expression of cathepsin K, interleukin-34, and bone morphogenetic protein-6. Quiescent osteoclast precursors increased significantly in spleen 2 days following bleeding, whereas osteoclast activity remained unchanged up to 2 weeks postbleeding. Osteoclast-dependent B-cell differentiation was affected at the pre-B stage of maturation in BM, whereas the Lin(-)Sca-1(+)c-kit(+) population expanded in BM and spleen after 2 days postbleeding. Our data demonstrate that an acute blood loss promotes differentiation and maturation of osteoclasts at 1 week but does not enhance osteoresorption at 2 weeks postbleeding. Our data also identify osteoclast differentiation as a consequent and important event in establishing HSC homeostasis following hematopoietic stress. (C) 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.