Kruppel-like factor 4 regulates metalloproteinase and aggrecanasegene expression in chondrocytes
Kruppel-like factor 4 regulates metalloproteinase and aggrecanasegene expression in chondrocytes
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Kruppel 样因子 4 调节软骨细胞中金属蛋白酶和聚集蛋白聚糖酶基因的表达
DOI：
10.1007/s00441-017-2674-0
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Fujikawa et al.
中科院分区：
文献类型：
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作者：
Takeuchi Y.;Tatsuta S.;Kito A.;Fujikawa J.;Itoh S.;Itoh Y.;Akiyama S.;Yamashiro T.;Wakisaka S.;Abe M.;Takeuchi et al.;Yamauchi et al.;Fujikawa et al.
Kruppel样因子4（KLF 4）是一种锌指转录因子，在多个器官的发育和维持过程中起着至关重要的作用。我们和其他人以前已经表明，KLF 4参与骨建模和重塑，但KLF 4在骨骼发生过程中发挥的作用仍然没有完全了解。在这里，我们表明，KLF 4表达在骺生长板和关节软骨细胞。大多数关节软骨细胞表达KLF 4的胚胎，但它只局限于一个子集的表浅区细胞在出生后的小鼠。当KLF 4在体外软骨细胞中过表达时，它严重抑制软骨细胞基因表达。KLF 4转导的软骨细胞的全球基因表达谱显示基质金属蛋白酶和去整合素和金属蛋白酶的基质降解蛋白酶与血小板反应蛋白-1结构域家族在上调基因组内。KLF 4诱导的蛋白酶被曲古抑菌素A处理减轻，这表明KLF 4诱导蛋白酶的表观遗传机制可能参与其中。这些结果表明KLF 4可能参与软骨发育和维持过程中的生理和病理方面。
Kruppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays crucial roles during the development and maintenance of multiple organs. We and others have previously shown that KLF4 is involved in bone modeling and remodeling but roles played by KLF4 during skeletogenesis are still not fully understood. Here, we show that KLF4 is expressed in the epiphyseal growth plate and articular chondrocytes. Most articular chondrocytes expressed KLF4 in embryos but it localized only in a subset of superficial zone cells in postnatal mice. When KLF4 was overexpressed in chondrocytes in vitro, it severely repressed chondrocytic gene expressions. Global gene expression profiling of KLF4-transduced chondrocytes revealed matrix degrading proteinases of the matrix metalloproteinase and disintegrin and metalloproteinase with thrombospondin-1 domain families within the group of upregulated genes. Proteinase induction by KLF4 was alleviated by Trichostatin A treatment suggesting the possible involvement of epigenetic mechanisms on proteinase induction by KLF4. These results indicate the possible involvement of KLF4 in physiological and pathological aspects during cartilage development and maintenance.