Immature and Mature Megakaryocytes Enhance Osteoblast Proliferation and Inhibit Osteoclast Formation
Immature and Mature Megakaryocytes Enhance Osteoblast Proliferation and Inhibit Osteoclast Formation
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DOI：
10.1002/jcb.22456
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Kacena, Melissa A.
中科院分区：
文献类型：
--
作者：
Ciovacco, Wendy A.;Cheng, Ying-Hua;Kacena, Melissa A.
最近的数据表明，巨核细胞（mk）在骨骼稳态中发挥作用。体外和体内数据显示，mk刺激成骨细胞（OB）增殖，抑制成骨细胞（OC）形成，从而有利于净骨沉积。有几种小鼠模型具有巨核生成失调和由此产生的高骨量表型。我们小组广泛研究的一个这样的模型是GATA-1缺陷小鼠。GATA-1是正常巨核生成所需的转录因子，缺乏GATA-1的小鼠未成熟MK数量增加，骨量显著增加。虽然骨量的增加可能仅仅是MK数量增加的结果，但在这里，我们对这些小鼠的MK进行了更深入的研究，看看是否有一个独特的因素固有于GATA-1缺陷的MK，有利于增加骨沉积。我们发现，MK数量的增加与OB增殖的增加和DC形成的减少相对应，成熟阶段的线索不会改变MK对巨核细胞阶段以后骨细胞系的影响，并且GATA-1缺陷MK比野生型对照存活的时间更长。因此，虽然GATA-1缺陷小鼠的MK数量增加可能导致高骨量表型，但我们认为该谱系的寿命延长也起作用。由于GATA-1缺陷的mk寿命更长，它们能够对OBs发挥更大的增殖作用，对OCs发挥更大的抑制作用。j .细胞。中国生物医学工程学报，2009,31(2):444 - 444。(C) 2010 Wiley-Liss, Inc。
Recent data suggest that megakaryocytes (MKs) play a role in skeletal homeostasis. In vitro and in vivo data show that MKs stimulate osteoblast (OB) proliferation and inhibit osteoelast (OC) formation, thus favoring net bone deposition. There are several mouse models with dysregulated megakaryopoiesis and resultant high bone mass phenotypes. One such model that our group has extensively studied is GATA-1 deficient mice. GATA-1 is a transcription factor required for normal megakaryopoiesis, and mice deficient in GATA-1 have increases in immature MK number and a striking increase in bone mass. While the increased bone mass could simply be a result of increased MK number, here we take a more in depth look at the MKs of these mice to see if there is a unique factor inherent to GATA-1 deficient MKs that favors increased bone deposition. We show that increased MK number clues correspond with increased OB proliferation and decreased DC formation that stage of maturation clues not alter the effect of MKs on bone cell lineages beyond the megakaryoblast stage, and that GATA-1 deficient MKs survive longer than wild-type controls. So while increased MK number in GATA-1 deficient mice likely contributes to the high bone mass phenotype, we propose that the increased longevity of this lineage also plays a role. Since GATA-1 deficient MKs live longer they are able to exert both more proliferative influence on OBs and more inhibitory influence on OCs. J. Cell. Biochem. 109: 774-781, 2010. (C) 2010 Wiley-Liss, Inc.