Chen Julia C, Hoey David A, Chua Mardonn, Bellon Raymond, Jacobs Christopher R
*Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada.
*Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada
FASEB J. 2016 Apr;30(4):1504-11. doi: 10.1096/fj.15-276402. Epub 2015 Dec 16.
It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitmentin vitro In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for the first time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cellsin vivo Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitmentin vivoand that the primary cilium contributes to this process.-Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism.
长期以来一直有人怀疑，但从未直接证实，为适应机械负荷增加而形成的骨与骨骼干细胞产生成骨细胞有关。的确，生物物理刺激在体外能有效调节成骨细胞系的定向分化。在本研究中，我们移植了表达绿色荧光蛋白的骨髓细胞以进行谱系追踪，并对小鼠施加生物物理刺激以引发骨形成反应。我们检测到移植祖细胞来源的细胞嵌入到响应负荷的活跃骨形成表面附近的骨基质中，首次证明机械信号增强了骨髓细胞在体内归巢并附着于骨表面以及这些细胞向成骨细胞系的定向分化。此外，我们使用诱导型Cre/Lox重组系统在移植细胞及其后代中随意删除驱动蛋白家族成员3A（Kif3a），该基因对初级纤毛形成至关重要，无论哪些组织可能已整合了这些细胞。破坏祖细胞群体中的机械传感细胞器——初级纤毛，显著减少了响应机械刺激而形成的骨量。我们研究的总体结果直接表明，在一个新的实验性干细胞力学生物学模型中，机械信号在体内增强成骨细胞系的定向分化，并且初级纤毛有助于这一过程。——陈，J.C.，霍伊，D.A.，蔡，M.，贝隆，R.，雅各布斯，C.R.机械信号通过初级纤毛介导的机制促进成骨命运。
