(A) Generation of CTGF-deficient (CTGF-def) Raw264.7 cells using the CRISPR-Cas9 technique. Expression of CTGF was determined by immunoblotting. (B, C) WT or CTGF-def Raw264.7 macrophages were transfected with pcDNA-ADAMTS12 (pcDNA-TS12) for 48hrs, then cells were treated with or without IL-1β for the indicated time. Cells were isolated to determine the phosphorylation of p65, p38 and JNK and the expression level of TS12 (B), or expression of NOS-2 and TS12 (C) by immunoblotting. (D–F) WT or CTGF-def Raw264.7 cells were transfected with pcDNA-ADAMTS12 (pcDNA-TS12) for 48hrs, then cells were treated with or without IL-1β. Transcriptional expression level of Il-6, NOS-2, and COX-2 were evaluated by real-time PCR. Values are means ± SD. *p<0.05, **p < 0.01 versus control group. Unless noted, n=3.