Megakaryocytes are mechanically responsive and influence osteoblast proliferation and differentiation.
Megakaryocytes are mechanically responsive and influence osteoblast proliferation and differentiation.
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DOI：
10.1016/j.bone.2014.05.015
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发表时间：
2014-09
期刊：
影响因子：
4.1
通讯作者：
Goldstein, Steven A.
中科院分区：
文献类型：
--
作者：
Soves, Constance P.;Miller, Joshua D.;Begun, Dana L.;Taichman, Russell S.;Hankenson, Kurt D.;Goldstein, Steven A.
骨量和骨几何结构的维持受机械刺激的影响。范例表明，包埋在矿化基质内的骨细胞以及骨表面的成骨细胞是对物理力的主要应答细胞。然而，骨髓腔内的其他细胞，如巨核细胞（MKs），也受到机械力的作用。近期研究强调了巨核细胞对体内成骨细胞增殖以及骨形成的强大作用。我们假设巨核细胞能够对物理力作出反应，并且这些细胞与成骨细胞之间的相互作用会受到机械刺激的影响。
在这项研究中，我们证明两种巨核细胞系在培养时对流体剪切应力有反应。此外，利用激光捕获显微切割技术，我们从体内承受压缩负荷的小鼠胫骨组织切片中分离出巨核细胞。C - fos是一种转录因子，已表明在多种组织类型中会因负荷而上调，在承受负荷的肢体的巨核细胞中，其表达量相对于未承受负荷的肢体有所增加，增加水平与来自同一肢体的骨细胞相当。我们还开发了一种共培养系统，以研究培养中的巨核细胞受到机械刺激是否会影响成骨细胞的增殖和分化。在共培养中，巨核细胞的存在（而非条件培养基）对培养的前成骨细胞MC3T3 - E1细胞的增殖具有显著影响。我们的数据表明，与未受刺激的巨核细胞共培养相比，与受剪切力作用的巨核细胞共培养的成骨细胞增殖略有降低，但矿化能力有所提高。
Maintenance of bone mass and geometry is influenced by mechanical stimuli. Paradigms suggest that osteocytes embedded within the mineralized matrix and osteoblasts on the bone surfaces are the primary responders to physical forces. However, other cells within the bone marrow cavity, such as megakaryocytes (MKs), are also subject to mechanical forces. Recent studies have highlighted the potent effects of MKs on osteoblast proliferation as well as bone formation in vivo. We hypothesize that MKs are capable of responding to physical forces and that the interactions between these cells and osteoblasts can be influenced by mechanical stimulation. In this study, we demonstrate that two MK cell lines respond to fluid shear stress in culture. Furthermore, using laser capture microdissection, we isolated MKs from histologic sections of murine tibiae that were exposed to compressive loads in vivo. C-fos, a transcription factor shown to be upregulated in response to load in various tissue types, was increased in MKs from loaded relative to non-loaded limbs at a level comparable to that of osteocytes from the same limbs. We also developed a co-culture system to address whether mechanical stimulation of MKs in culture would impact osteoblast proliferation and differentiation. The presence of MKs in co-culture, but not conditioned media, had dramatic effects on proliferation of preosteoblast MC3T3-E1 cells in culture. Our data suggests a minimal decrease in proliferation as well as an increase in mineralization capacity of osteoblasts co-cultured with MKs exposed to shear compared to co-cultures with unstimulated MKs.
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