WNK2 regulates the response to hyperosmotic stress in chondrocytes

How chondrocytes of the synovial joint sense and respond to hyperosmotic stress to maintain joint homeostasis over time is undetermined. The With-No-Lysine (K) (WNK) protein kinases are major intracellular sensors of hyperosmotic stress that respond by regulating ion channel activity and signaling pathways. To determine if WNK2 is a hyperosmotic sensor in chondrocytes and to identify the genes and pathways regulated by WNK2, we examined the molecular response of chondrocytes to WNK2 overexpression and hyperosmotic stress. Overall design: To determine WNK2 function in osteoarthritis, we used CRISPR/Cas9 to delete exon 2 of WNK2 in the T/C-28a2 human chondrocyte cell line by designing two gRNA around exon 2. We then perfomed gene expression profiling analysis using data obtained from RNA-seq of wildtype and WNK2 deleted T/C-28a2 cells at 4 different conditions (Control, Sorbitol, WNK2 overexpression, Sorbitol+WNK2 overexpression)