Vinall Ruth L, Lo Su Hao, Reddi A Hari
Center for Tissue Regeneration and Repair, University of California Davis, Sacramento, California 95817, USA.
Exp Cell Res. 2002 Jan 1;272(1):32-44. doi: 10.1006/excr.2001.5395.
Bone morphogenetic proteins (BMPs) induce cartilage differentiation and morphogenesis. There are profound changes in the cytoskeletal architecture during the morphogenesis of cartilage. To investigate the possibility that morphogenetic signals such as BMPs may regulate chondrocyte phenotype by modulation of cytoskeletal protein expression, we determined whether the expression and distribution of cytoskeletal proteins in chondrocytes are regulated by bone morphogenetic protein 7 (BMP 7), interleukin 1 (IL-1), and cellular context. Addition of BMP 7, a morphogen that induces chondrogenesis, to primary cultures of bovine and murine chondrocytes induced increased expression of four cytoskeletal proteins: tensin, talin, paxillin, and focal adhesion kinase (FAK). The expression of cytoskeletal proteins is dependent on cellular context; compared to monolayer, chondrocytes in suspension exhibited increased expression of cytoskeletal components. Conversely, addition of IL-1, a catabolic cytokine, induced loss of chondrocyte phenotype and decreased the expression of these cytoskeletal components. Treatment of chondrocytes with cytochalasin D (an agent that disrupts the actin cytoskeleton) inhibited BMP 7-induced upregulation of tensin, talin, paxillin, and FAK, and blocked the effect of BMP 7 on chondrocyte phenotype. Taken together these data demonstrate that cytoskeletal components play a critical role in the response to morphogens and cytokines in the regulation of chondrocyte phenotype. (c)2001 Elsevier Science.
骨形态发生蛋白（BMPs）可诱导软骨分化和形态发生。在软骨形态发生过程中，细胞骨架结构会发生深刻变化。为了研究诸如BMPs等形态发生信号是否可能通过调节细胞骨架蛋白表达来调控软骨细胞表型，我们确定了软骨细胞中细胞骨架蛋白的表达和分布是否受骨形态发生蛋白7（BMP 7）、白细胞介素1（IL-1）及细胞环境的调控。向牛和小鼠软骨细胞原代培养物中添加诱导软骨形成的形态发生素BMP 7，可诱导四种细胞骨架蛋白（张力蛋白、踝蛋白、桩蛋白和粘着斑激酶（FAK））的表达增加。细胞骨架蛋白的表达取决于细胞环境；与单层培养相比，悬浮培养的软骨细胞中细胞骨架成分的表达增加。相反，添加分解代谢细胞因子IL-1会导致软骨细胞表型丧失，并降低这些细胞骨架成分的表达。用细胞松弛素D（一种破坏肌动蛋白细胞骨架的试剂）处理软骨细胞，可抑制BMP 7诱导的张力蛋白、踝蛋白、桩蛋白和FAK的上调，并阻断BMP 7对软骨细胞表型的影响。综上所述，这些数据表明细胞骨架成分在软骨细胞表型调控中对形态发生素和细胞因子的反应中起关键作用。（c）2001爱思唯尔科学出版社。
