Integrins on joint cartilage chondrocytes and alterations by ofloxacin or magnesium deficiency in immature rats.
Recently, we showed that magnesium deficiency induces lesions in knee joint cartilage from 5-week-old rats that are very similar to ofloxacin-induced cartilage defects. We concluded that quinolone-induced arthropathy is probably due to chelation of magnesium and thus a deficit in functionally available magnesium in joint cartilage (Stahlmann et al. 1995). As magnesium deficiency in joint cartilage could impair chondrocyte-matrix interaction which is mediated by cation-dependent integrin receptors of the beta 1-subfamily, we investigated integrin expression in joint cartilage from untreated, ofloxacin-treated and magnesium-deficient Wistar rats. With immunohistochemical methods using monoclonal and polyclonal antibodies, we showed that the integrin pattern in joint cartilage from rats corresponded largely to integrin expression described for human cartilage tissue: beta 1, alpha 1, alpha 3 and alpha v subunits and the alpha 5 beta 1 and alpha v beta 3 heterodimers were consistently expressed. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2 x 600 mg ofloxacin/kg for 1 day. Gross-structural lesions (e.g., cleft formation, unmasked collagen fibres) in magnesium-deficient rats were very similar but changes in integrin expression were less pronounced. On the other hand, changes in cartilage matrix composition showed similar alterations in ofloxacin-treated and magnesium-deficient rats: fibronectin deposition in the cartilage matrix increased in both groups while glycosaminoglycan content decreased. In summary, similar defects occur in ofloxacin-treated and magnesium-deficient rats and with immunohistochemical methods subtle differences are demonstrable.
Förster
C
C
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Germany.
Kociok
K
K
Shakibaei
M
M
Merker
H J
HJ
Vormann
J
J
Günther
T
T
Stahlmann
R
R
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000378:metabolism* / Q000473:pathology; D008854:Microscopy, Electron; D015242:Ofloxacin / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D016023:Integrins; D015242:Ofloxacin; D002118:Calcium