Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis.
Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain and a progressive loss of articular cartilage. Studies to elucidate the pathophysiology of OA have been hampered by the lack of a rapid, reproducible animal model that mimics both the histopathology and symptoms associated with the disease. Injection of mono-iodoacetate (MIA), an inhibitor of glycolysis, into the femorotibial joint of rodents promotes loss of articular cartilage similar to that noted in human OA. Here, we describe the histopathology in the subchondral bone and cartilage of rat (Wistar) knee joints treated with a single intra articular injection of MIA (1 mg) and sacrificed at 1, 3, 5, 7, 14, 28, and 56 days postinjection. Histologically, the early time points (days 1-7) were characterized by areas of chondrocyte degeneration/necrosis sometimes involving the entire thickness of the articular cartilage in the tibial plateaus and femoral condyles. Changes to the subchondral bone, as evidenced by increased numbers of osteoclasts and osteoblasts, were noted at by day 7. By 28 days, there was focal fragmentation and collapse of bony trabeculae with fibrosis and increased osteoclastic activity. By 56 days there were large areas of bone remodeling evidenced by osteoclastic bone resorption and newly formed trabeculae with loss of marrow hematopoietic cells. Subchondral cysts and subchondral sclerosis were present in some rats. In conclusion, intra-articular injection of MIA induces loss of articular cartilage with progression of subchondral bone lesions that mimic those of OA. This model offers a rapid and minimally invasive method to reproduce OA-like lesions in a rodent species.
Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. roberto.guzman@pfizer.com
Roberto E
RE
Guzman
Mark G
MG
Evans
Susan
S
Bove
Brandy
B
Morenko
Kenneth
K
Kilgore
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000473:pathology*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005270:Femur Head / Q000187:drug effects / Q000473:pathology; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007270:Injections, Intra-Articular; D007461:Iodoacetates / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects / Q000473:pathology
D004791:Enzyme Inhibitors; D007461:Iodoacetates