ab2005

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

J. Eguchi, T. Koshino, T. Takagi, T. Hayashi, T. Saito

Department of Orthopaedic Surgery, Yokohama City University School of Medicine,
Yokohama, Japan.

ABSTRACT
Objective
To investigate the roles of NF-kB and I-kB 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-kB and anti-I-kB antibodies was performed to observe the expression and nuclear shift of NF-kB and I-kB 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-kB-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-kB-positive nuclei was 9.1 ± 0.7, 19.5 ± 3.7, 47.5 ± 3.0 and 8.6 ± 0.1%, respectively. NF-kB-positive chondrocytes significantly increased from 3 to 7 weeks in a time-dependent manner (p < 0.0001). The percentage of I-kB-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-kB-positive chondrocytes significantly increased from 3 to 5 weeks (p < 0.005).

Conclusion
These findings suggest that nuclear shift of NF-kB localization causes cartilage destruction in the early stage of arthritis in DBA/1 mice immunized with C II.

Key words
NF-kB, I-kB, collagen-induced arthritis, DBA/1 mouse, cartilage destruction.

Please address correspondence and reprint requests to: Dr. Jun Eguchi, Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Fukuura 3-9 Kanazawa-ku, Yokohama 236-0004, Japan.