Primary Cilia Exhibit Mechanosensitivity to Cyclic Tensile Strain and Lineage-Dependent Expression in Adipose-Derived Stem Cells
Primary Cilia Exhibit Mechanosensitivity to Cyclic Tensile Strain and Lineage-Dependent Expression in Adipose-Derived Stem Cells
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DOI：
10.1038/s41598-019-43351-y
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发表时间：
2019-05-29
影响因子：
4.6
通讯作者：
Loboa, Elizabeth G.
中科院分区：
文献类型：
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作者：
Bodle, Josephine;Hamouda, Mehdi S.;Loboa, Elizabeth G.
非运动性初级纤毛是一种动态的细胞感觉结构，在脂肪来源的干细胞(ASCs)中表达，我们先前已经证明初级纤毛参与了体外化学诱导人ASC的成骨分化。此外，我们已经报道了10%的循环拉伸应变(1赫兹，每天4小时)促进了HASC的成骨。我们假设初级纤毛以谱系依赖的方式对循环拉伸应变作出反应，并且它们的机械敏感性可能调节定位于纤毛的信号通路的动态。我们发现，HASC的形态、纤毛长度和纤毛形态因在完全生长、成骨分化或成脂分化培养液中培养的不同而不同，最长的纤毛在成脂分化细胞中表达。进一步，我们发现，循环拉伸应变既促进了hASCs的成骨分化，又抑制了成脂分化，分别表现为RUNX2基因的表达上调和PPARG和IGF-1的下调。这项研究表明，HASC初级纤毛对循环拉伸应变和谱系依赖的表达表现出机械敏感性，这可能在一定程度上调节了分化过程中定位于初级纤毛的信号通路。我们强调了初级纤毛结构在机械传感和谱系确定中的重要性，并推测这种结构可能是组织工程应用中操纵HASC的一个新靶点。
Non-motile primary cilia are dynamic cellular sensory structures and are expressed in adipose-derived stem cells (ASCs).We have previously shown that primary cilia are involved in chemically-induced osteogenic differentiation of human ASC (hASCs) in vitro. Further, we have reported that 10% cyclic tensile strain (1Hz, 4 hours/day) enhances hASC osteogenesis. We hypothesize that primary cilia respond to cyclic tensile strain in a lineage dependent manner and that their mechanosensitivity may regulate the dynamics of signaling pathways localized to the cilium. We found that hASC morphology, cilia length and cilia conformation varied in response to culture in complete growth, osteogenic differentiation, or adipogenic differentiation medium, with the longest cilia expressed in adipogenically differentiating cells. Further, we show that cyclic tensile strain both enhances osteogenic differentiation of hASCs while it suppresses adipogenic differentiation as evidenced by upregulation of RUNX2 gene expression and downregulation of PPARG and IGF-1, respectively. This study demonstrates that hASC primary cilia exhibit mechanosensitivity to cyclic tensile strain and lineage-dependent expression, which may in part regulate signaling pathways localized to the primary cilium during the differentiation process. We highlight the importance of the primary cilium structure in mechanosensing and lineage specification and surmise that this structure may be a novel target in manipulating hASC for in tissue engineering applications.