AG-041R, a cholecystokinin-B/gastrin receptor antagonist, stimulates the repair of osteochondral defect in rabbit model.
A newly synthesized compound (AG-041R), 3R-1-(2,2Diethoxyethyl)-((4methylphenyl) amino-carbonyl methyl)-3-((4methylphenyl) ureido-indoline-2-one), is a cholecystokinin-B/gastrin receptor antagonist which has stimulatory effects on the matrix synthesis of chondrocytes in vitro. In this study, we examined the effect of AG-041R on the repair of osteochondral defects (cylindrical, 4 mm diameter) in the patellar groove of the rabbit knee joint. At the time of operation, 100 microl of 1 microM of AG-041R was administered, followed by 200 microl with an osmotic pump for 14 days. Histological and biochemical evaluations were performed at 12 and 24 weeks after surgery. The histological score of the AG-041R-treated group, the quantity of glycosaminoglycan and the ratio of chondroitin sulfate in the AG-041R-treated tissue were significantly higher than in the untreated group. Moreover, the degeneration of cartilage around the defect was suppressed in the AG-041R-treated group. These findings suggest that AG-041R is effective for the repair of osteochondral defects.
Nakanishi
Toru
T
Department of Orthopaedics, Shimane Medical University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
Kawasaki
Kenzo
K
Uchio
Yuji
Y
Kataoka
Hiroko
H
Terashima
Masaharu
M
Ochi
Mitsuo
M
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D002809:Chondroitin Sulfates / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D011817:Rabbits; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects*
C109755:AG-041R; D006025:Glycosaminoglycans; D007211:Indoles; D011949:Receptors, Cholecystokinin; D002809:Chondroitin Sulfates