Connective tissue growth factor in regulation of RhoA mediated cytoskeletal tension associated osteogenesis of mouse adipose-derived stromal cells.
Connective tissue growth factor in regulation of RhoA mediated cytoskeletal tension associated osteogenesis of mouse adipose-derived stromal cells.
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DOI：
10.1371/journal.pone.0011279
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发表时间：
2010-06-23
期刊：
影响因子：
3.7
通讯作者：
Longaker MT
中科院分区：
文献类型：
--
作者：
Xu Y;Wagner DR;Bekerman E;Chiou M;James AW;Carter D;Longaker MT
细胞骨架张力是一种细胞内机制，细胞通过该机制将机械信号转化为生化反应，包括细胞因子的产生和各种信号传导途径的激活。通过以低密度（1,250 个细胞/cm2）接种，使脂肪源性基质细胞（ASC）扩散成大细胞，观察到这会诱导成骨。相反，以高密度（25,000 个细胞/cm2）接种的 ASC 具有促进脂肪生成的小细胞。 RhoA 和肌动蛋白丝因细胞大小的变化而改变。细胞松弛素 D 阻断肌动蛋白聚合会影响细胞骨架张力和 ASC 的分化。为了了解导致肌动蛋白细胞骨架张力的潜在调节机制，对大型和小型 ASC 进行了 cDNA 微阵列分析。结缔组织生长因子 (CTGF) 被认为是与 RhoA 介导的细胞骨架张力相关的成骨的主要调节剂。随后，ASC 中 siRNA 敲低 CTGF 抑制了这种成骨作用。我们得出结论，CTGF 在调节细胞骨架张力介导的 ASC 成骨分化中很重要。
Cytoskeletal tension is an intracellular mechanism through which cells convert a mechanical signal into a biochemical response, including production of cytokines and activation of various signaling pathways. Adipose-derived stromal cells (ASCs) were allowed to spread into large cells by seeding them at a low-density (1,250 cells/cm2), which was observed to induce osteogenesis. Conversely, ASCs seeded at a high-density (25,000 cells/cm2) featured small cells that promoted adipogenesis. RhoA and actin filaments were altered by changes in cell size. Blocking actin polymerization by Cytochalasin D influenced cytoskeletal tension and differentiation of ASCs. To understand the potential regulatory mechanisms leading to actin cytoskeletal tension, cDNA microarray was performed on large and small ASCs. Connective tissue growth factor (CTGF) was identified as a major regulator of osteogenesis associated with RhoA mediated cytoskeletal tension. Subsequently, knock-down of CTGF by siRNA in ASCs inhibited this osteogenesis. We conclude that CTGF is important in the regulation of cytoskeletal tension mediated ASC osteogenic differentiation.
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