The shear force effect on human chondrocytes is time and magnitude dependent. Recently, kruppel-like factor (KLF) 4 has been identified as a pleiotropic protein and its activity in cells is dependent on different stimuli and/or cell types. The role of KLF4 in chondrocytes is still unclear and there has been no report determining whether shear force regulates KLF4 levels in chondrocytes. Hence, this study was carried out to investigate the role of KLF4 in human chondrocytes under shear force stimulation and the underlying mechanism. Human primary and SW1353 chondrocytes were used in this study. The shear forces at 2, 5, or 15 dyn/cm2 intensity were applied to both types of human chondrocytes. The specific small interfering RNAs, activators, and inhibitors were used to study the detailed mechanism of shear force. The presented results showed that 2, but not 5 and 15, dyn/cm2 shear force increases KLF4 expression in human primary and SW1353 chondrocytes. Extracellular signal-regulated kinase 5 induced peroxisome proliferator-activated receptor γ transcription activity to increase KLF4 transcription. Moreover, the KLF4 induction in human chondrocytes in response to 2 dyn/cm2 shear force could attenuate interleukin (IL)-1β-stimulated nuclear factor-κB activation. These results elucidate the role of KLF4 in antagonizing the effect of IL-1β in human chondrocytes under 2 dyn/cm2 shear force stimulation and provide a possible mechanism to demonstrate the protection of moderate forces or exercises in cartilage.
Keywords: chondrocytes; extracellular signal-regulated kinase 5 (ERK5); kruppel-like factor 4 (KLF4); peroxisome proliferator-activated receptor γ (PPARγ); shear stress.
© 2018 Wiley Periodicals, Inc.