ab2006

Corticosteroid treatment induces chondrocyte apoptosis in an experimental arthritis model and in chondrocyte cultures

F. Nakazawa, H. Matsuno, K. Yudoh, Y. Watanabe¹, R. Katayama, T. Kimura

Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, Toyama; ¹Department of Clinical Biochemistry, Hokkaido Institute of Pharmaceutical Sciences, Katsuraoka, Japan.

ABSTRACT
Object
In order to examine the mechanisms involved in steroid-induced arthropathy after intra-articular corticosteroid injection, a histological examination was performed in vivo using severe combined immunodeficiency (SCID) mice that were implanted with human articular cartilage into the back (SCID/hu model). In addition, the effect of corticosteroids on chondrocyte apoptosis was evaluated in vitro using cultured human chondrocytes.

Method
Human articular cartilage was obtained during knee surgery and implanted subcutaneously into the backs of SCID mice. One month later, weekly injections of corticosteroid (hydrocortisone acatate: 1mg/0.2ml, triamcinolone acetonide: 0.2mg/0.2ml, dexamethasone acetate: 0.1mg/0.2ml) in the subcutaneous cavity around the grafted cartilage in SCID mice were initiated. After six weeks of treatment, the grafted cartilage pieces were removed from the SCID mice and examined histologically. Chondrocyte apoptosis after corticosteroid treatment was also investigated using cultured human chondrocytes.

Result
In the corticosteroid treated, grafted articular cartilage, apoptotic chondrocytes were apparent in the superficial and middle layers of cartilage. But a reduced intensity of Safranin O staining was not remarkable. In the cultured chondrocytes, apoptotic changes were also observed after corticosteroid treatment.

Conclusion
Corticosteroid treatment induces chondrocyte apoptosis and it may be important to understand the steroid-induced arthropathy.

Key words
Corticosteroid, apoptosis, chondrocyte, SCID/hu model.

Please address correspondence and reprint requests to: Fujio Nakazawa MD, Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
E-mail: SNA08804@nifty.com