Department of Oral Anatomy and Developmental Biology, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Osaka University Dental Hospital Division of Special Care Dentistry, Osaka, Japan.
Cell Tissue Res. 2017 Dec;370(3):441-449. doi: 10.1007/s00441-017-2674-0. Epub 2017 Aug 31.
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.
Kruppel 样因子 4（KLF4）是一种锌指转录因子，在多个器官的发育和维持中发挥着关键作用。我们和其他人之前已经表明，KLF4 参与了骨建模和重塑，但 KLF4 在骨骼发生过程中所扮演的角色仍不完全清楚。在这里，我们表明 KLF4 在骺板生长板和关节软骨细胞中表达。大多数关节软骨细胞在胚胎中表达 KLF4，但在出生后的小鼠中，它仅定位于浅层区细胞的一部分。当 KLF4 在体外过度表达于软骨细胞时，它严重抑制了软骨细胞基因的表达。对 KLF4 转导的软骨细胞进行全基因组表达谱分析显示，在上调基因的一组中，存在基质金属蛋白酶和整合素金属蛋白酶与血小板反应蛋白-1 结构域家族的基质降解蛋白酶。用 Trichostatin A 处理可减轻 KLF4 诱导的蛋白酶，表明蛋白酶诱导可能涉及 KLF4 的表观遗传机制。这些结果表明 KLF4 可能参与软骨发育和维持过程中的生理和病理方面。
