Author/Editor     De Bri, Edin; Lei, Wei
Title     Biochemical and histological effects of tetracyclines on spontaneous osteoarthritis in guinea pigs
Type     članek
Source     Image Anal Stereol
Vol. and No.     Letnik 19, št. 2
Publication year     2000
Volume     str. 125-31
Language     eng
Abstract     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 been shown 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 the guinea pig OA model. OA changes were most severe in the central compartment of 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 all tetracyclines, can reduce the severity of OA in the guinea pig model of spontaneous OA.
Descriptors     OSTEOARTHRITIS
TETRACYCLINE
CARTILAGE, ARTICULAR
GUINEA PIGS
HISTOLOGICAL TECHNIQUES
ADMINISTRATION, ORAL
METALLOPROTEINASES
DISEASE MODELS, ANIMAL