A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells.
A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells.
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DOI：
10.1016/j.bbrc.2011.07.072
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发表时间：
2011-08-19
影响因子：
3.1
通讯作者：
Jacobs, Christopher R.
中科院分区：
文献类型：
--
作者：
Hoey, David A.;Kelly, Daniel J.;Jacobs, Christopher R.
骨转换是一个机械调节的过程，部分由驻留在组织内的机械敏感的骨细胞网络协调。间充质来源的成骨细胞的募集和成骨活性由许多因素决定，包括机械负荷。因此，令人惊讶的是，尽管协调的骨细胞和间充质干细胞(MSCs)之间存在机械调节的信号转导，但到目前为止还没有直接证实。本研究收集机械刺激的骨细胞条件培养液(MLO-Y4细胞)，加入MSCs(C3H10T1/2细胞)。加入机械刺激的骨细胞条件培养液，与静态培养的条件培养液相比，MSCs成骨基因OPN和COX2的表达显著上调，显示了两种细胞之间新的旁分泌信号机制。相同的机械条件培养液不改变成骨细胞(MC3T3细胞系)的基因表达，机械刺激的成骨细胞条件培养液也不改变MSCs的基因表达，表明该信号是骨细胞和MSCs所特有的。最后，如果在机械刺激骨细胞之前抑制初级纤毛的形成，则没有观察到MSCs成骨基因的上调。综上所述，本研究结果表明，骨细胞在机械刺激下分泌的可溶性因子可以增强MSCs成骨基因的表达，显示了一种新的、独特的信号机制，并引入了初级纤毛在骨中流动介导的旁分泌信号中的作用，从而突出了纤毛作为促进骨形成的治疗的潜在靶点。
Bone turnover is a mechanically regulated process, coordinated in part by the network of mechanosensitive osteocytes residing within the tissue. The recruitment and bone forming activity of the mesenchymal derived osteoblast is determined by numerous factors including mechanical loading. It is therefore somewhat surprising that although mechanically regulated signaling between the coordinating osteocytes and mesenchymal stem cells (MSCs) should exist, to date it has not been directly demonstrated. In this study, conditioned media from mechanically stimulated osteocytes (MLO-Y4 cell line) was collected and added to MSCs (C3H10T1/2 cell line). The addition of mechanically stimulated osteocyte conditioned media resulted in a significant upregulation of the osteogenic genes OPN and COX2 in MSCs compared to statically cultured conditioned media, demonstrating a novel paracrine signaling mechanism between the two cell types. The same mechanically conditioned media did not alter gene expression in osteoblasts (MC3T3 cell line), and mechanically stimulated osteoblast conditioned media did not alter gene expression in MSCs demonstrating that this signaling is unique to osteocytes and MSCs. Finally, the upregulation in osteogenic genes in MSCs was not observed if primary cilia formation was inhibited prior to mechanical stimulation of the osteocyte. In summary, the results of this study indicate that soluble factors secreted by osteocytes in response to mechanical stimulation can enhance osteogenic gene expression in MSCs demonstrating a novel, unique signaling mechanism and introduces a role for the primary cilium in flow mediated paracrine signaling in bone thereby highlighting the cilium as a potential target for therapeutics aimed at enhancing bone formation.
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影响因子：
4.1
作者：
You, Lidan;Temiyasathit, Sara;Jacobs, Christopher R.
通讯作者：
Jacobs, Christopher R.
影响因子：
6.2
作者：
Kitase, Yukiko;Barragan, Leonardo;Qing, Hai;Kondoh, Shino;Jiang, Jean X.;Johnson, Mark L.;Bonewald, Lynda F.
通讯作者：
Bonewald, Lynda F.
影响因子：
3.3
作者：
Taulman, PD;Haycraft, CJ;Yoder, BK
通讯作者：
Yoder, BK
影响因子：
4.8
作者：
KLEINNULEND, J;VANDERPLAS, A;BURGER, EH
通讯作者：
BURGER, EH
影响因子：
15.9
作者：
Zhang, XP;Schwarz, EM;O'Keefe, RJ
通讯作者：
O'Keefe, RJ