Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells
Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells
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DOI：
10.1182/blood-2011-06-360933
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发表时间：
2012-03-15
期刊：
影响因子：
20.3
通讯作者：
Bellido, Teresita
中科院分区：
文献类型：
--
作者：
Calvi, Laura M.;Bromberg, Olga;Bellido, Teresita
造血干细胞（HSC）的微环境扩增是由甲状旁腺激素（PTH）或成骨细胞中PTH受体（PTH 1 R）的激活诱导的;然而，介导PTH这种作用的成骨细胞亚群尚不清楚。骨细胞是嵌入矿化骨基质中的终末分化成骨细胞，但与BM连接。骨细胞中PTH 1 R的活化增加成骨细胞数量和骨量。为了确定骨细胞介导的PTH 1 R信号传导是否扩增HSC，我们研究了在骨细胞中表达组成型活性PTH 1 R的小鼠（TG小鼠）。TG小鼠的成骨细胞、破骨细胞和骨小梁增加，而BM表型HSC或HSC功能没有变化。TG小鼠的骨小梁逐渐增加，但HSC功能下降。在严重受累的TG小鼠中，骨髓中的表型HSC减少，但脾脏中的表型HSC增加。TG骨细胞与微环境HSC支持相关的信号没有增加，并且在TG骨中不存在随着PTH治疗而增加的梭形成骨细胞。这些发现表明，骨细胞中PTH 1 R信号传导的激活不会扩增BM HSC，而是在TG小鼠中减少。因此，骨细胞不介导由PTH 1 R信号传导诱导的HSC扩增。此外，成骨细胞扩张不足以增加HSC。（血。2012; 119（11）：2489-2499）
Microenvironmental expansion of hematopoietic stem cells (HSCs) is induced by treatment with parathyroid hormone (PTH) or activation of the PTH receptor (PTH1R) in osteoblastic cells; however, the osteoblastic subset mediating this action of PTH is unknown. Osteocytes are terminally differentiated osteoblasts embedded in mineralized bone matrix but are connected with the BM. Activation of PTH1R in osteocytes increases osteoblastic number and bone mass. To establish whether osteocyte-mediated PTH1R signaling expands HSCs, we studied mice expressing a constitutively active PTH1R in osteocytes (TG mice). Osteoblasts, osteoclasts, and trabecular bone were increased in TG mice without changes in BM phenotypic HSCs or HSC function. TG mice had progressively increased trabecular bone but decreased HSC function. In severely affected TG mice, phenotypic HSCs were decreased in the BM but increased in the spleen. TG osteocytes had no increase in signals associated with microenvironmental HSC support, and the spindle-shaped osteoblastic cells that increased with PTH treatment were not present in TG bones. These findings demonstrate that activation of PTH1R signaling in osteocytes does not expand BM HSCs, which are instead decreased in TG mice. Therefore, osteocytes do not mediate the HSC expansion induced by PTH1R signaling. Further, osteoblastic expansion is not sufficient to increase HSCs. (Blood. 2012; 119(11):2489-2499)