Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation
Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation
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DOI：
10.1016/j.bbrc.2015.02.080
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发表时间：
2015-03-01
影响因子：
3.1
通讯作者：
Hoey, David A.
中科院分区：
文献类型：
--
作者：
Brady, Robert T.;O'Brien, Fergal J.;Hoey, David A.
骨形成需要间充质祖细胞的募集、增殖和成骨分化。驱动这一过程的一个强有力的刺激是机械负荷，但支持这一点的信号机制尚未完全理解。本研究的目的是探讨机械刺激的骨细胞和成骨细胞分泌蛋白在协调祖细胞对骨形成的贡献中的作用。最初，将骨细胞（MLO-Y 4）和成骨细胞（MC 3 T3）机械刺激24小时，收集条件培养基内的分泌因子，并用于评价间充质干细胞（MSC）和成骨细胞募集、增殖和成骨。与静态培养的骨细胞分泌的因子相比，机械刺激的骨细胞分泌的旁分泌因子显著增强MSC迁移、增殖和成骨，并且进一步显著增加成骨细胞迁移和增殖。其次，机械刺激的成骨细胞分泌的旁分泌因子显着增强MSC迁移，但令人惊讶的是，相反的骨细胞分泌，抑制MSC增殖相比，静态培养的成骨细胞分泌的因子。在成骨细胞中观察到类似的趋势。这项研究提供了骨中机械驱动信号机制的新信息，并强调了骨谱系不同阶段细胞之间的对比分泌组，进一步加深了我们对骨形成和骨祖细胞间接生物物理调节的理解。(C)2015爱思唯尔公司All rights reserved.
Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. (C) 2015 Elsevier Inc. All rights reserved.