Biochemical and histological effects of tetracyclines on spontaneous osteoarthritis in guinea pigs

english

2000

volume 19, issue 2

Osteoarthritis    therapy    Drug therapy    Tetracycline    Therapeutic use   Cartilage, articular   Chemistry    Anatomy and histology   Guinea pigs    Histological techniques    Administration, oral   Metalloproteinases    Antagonists and inhibitors   Disease models, animal

Društvo za stereologijo in kvantitativno analizo slike
(Obvezni izvod spletne publikacije)

Matrix metalloproteinases (MMPs) are mediators in connective tissue destruction in a variety of pathologic processes. Recently discovered chemically modified tetracyclines have been found to be effective inhibitors of MMP mediated connective tissue degradation in both rheumatoid arthritis (RA) and osteoarthritis (OA). The Hartley guinea pig model has been described with a high incidence of spontaneous OA-like changes in the knee joint. Therefore we have studied the effect of two tetracyclines, doxycycline (Dox) and chemically modified tetracycline-7 (CMT-7) which have both previously beenshown as potent MMP inhibitors. We found that prophylactic orally given CMT-7 decreases OA changes in the knee joints both in vitro and in vivo in theguinea pig OA model. OA changes were most severe in the central compartmentof the medial condyle in the control group. Cartilage fibrillation and destruction, in addition to subchondral bone sclerosis and cyst formation were all less in the CMT-7 treated group compared with controls. Collagen, hyaluronan and proteoglycan content in cartilage was higher in the CMT-7 treated group compared with controls. In contrast, OA changes were not decreased in the Dox group. These results show that tetracyclines, but not alltetracyclines, can reduce the severity of OA in the guinea pig model of spontaneous OA.

16.09.2009