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


METHODS
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: 1 mg/0.2 ml, triamcinolone acetonide: 0.2 mg/0.2 ml, dexamethasone acetate: 0.1 mg/0.2 ml) 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.


RESULTS
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.


CONCLUSIONS
Corticosteroid treatment induces chondrocyte apoptosis and it may be important to understand the steroid-induced arthropathy.
Nakazawa
F
F
Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, Toyama, Japan. SNA08804@nifty.com
Matsuno
H
H
Yudoh
K
K
Watanabe
Y
Y
Katayama
R
R
Kimura
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy / Q000473:pathology
D005938:Glucocorticoids