2 dyn/cm2 Shear Force Upregulates Kruppel-like Factor 4 Expression in Human Chondrocytes to Inhibit the Interleukin-1beta-activated NF-kappaB

[Speaker] Shun-Fu Chang:1
[Co-author] Kuo-Chin Huang:2, Cheng-Nan Chen:3
1:Department of Medical Research and Development, Chang Gung Memorial Hospital-Chiayi Branch, Taiwan, 2:Department of Orthopaedics, Chang Gung Memorial Hospital-Chiayi branch, Taiwan, 3:Department of Biochemical Science and Technology, National Chiayi University, Taiwan

Background. Kruppel-like factor (KLF) 4 has been indicated as a pleiotropic protein and its activity in cells is depended on different stimuli and/or cell types. The role of KLF4 in chondrocytes is still unclear and there is no report to determine whether shear force regulates KLF4 levels in chondrocytes. Hence, this study was to investigate the role of KLF4 in human chondrocytes under shear force stimulation and the underlying mechanism.

Methods. 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 siRNAs, activators and inhibitors were used to study the detailed mechanism of shear force.

Results. 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 gamma 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)-1beta-stimulated NF-kappaB activation.

Conclusions. This study demonstrates the KLF4 role in antagonizing IL-1beta effect in human chondrocytes under 2 dyn/cm2 shear force stimulation and provides a possible mechanism to elucidate the protection of moderate forces or exercises in cartilage.
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