NF-κB and I-κB overexpression in articular chondrocytes with progression of type II collagen-induced arthritis in DBA/1 mouse knees

Objective To investigate the roles of NF-kappaB and I-kappaB in chondrocytes in the cartilage destruction of mouse collagen-induced arthritis. Methods DBA/1 mice were immunized with bovine type II collagen (C II) emulsified with Freund's incomplete adjuvant. Histological abnormalities in the mouse knees were evaluated in sections stained with hematoxylin and eosin, or toluidine blue. Immunostaining using anti-NF-kappaB and anti-I-kappaB antibodies was performed to observe the expression and nuclear shift of NF-kappaB and I-kappaB in articular chondrocytes. Results Loss of metachromasia of perichondrial cartilage was found in 8 out of 10 knees of the mice at 5 weeks, and in all 10 knees at 7 weeks after C II-immunization. The mean percentage of NF-kappaB-positive chondrocytes at 3, 5 and 7 weeks and in the control was 33.6 +/- 7.6, 54.9 +/- 2.7, 75.9 +/- 1.0 and 27.9 +/- 3.8%, respectively. The mean percentage of NF-kappaB-positive nuclei was 9.1 +/- 0.7, 19.5 +/- 3.7, 47.5 +/- 3.0 and 8.6 +/- 0.1%, respectively. NF-kappaB-positive chondrocytes significantly increased from 3 to 7 weeks in a time-dependent manner (p < 0.0001). The percentage of I-kappaB-positive chondrocytes at 3, 5 and 7 weeks and in the control was 15.5 +/- 1.7, 41.1 +/- 2.5, 51.2 +/- 5.7 and 12.1 +/- 2.1%, respectively. I-kappaB-positive chondrocytes significantly increased from 3 to 5 weeks (p < 0.005). Conclusion These findings suggest that nuclear shift of NF-kappaB localization causes cartilage destruction in the early stage of arthritis in DBA/1 mice immunized with C II.