Effects of three antiarthritic drugs on fibronectin and keratan sulfate synthesis by cultured canine articular cartilage chondrocytes.
Because articular chondrocytes are a target for drugs that can influence the integrity of cartilage, we investigated the effects of 3 antiarthritic drugs, glycosaminoglycan polysulfate, diclofenac-Na, and S-adenosylmethionine sulfate p-toluenesulfonate on total protein, fibronectin, and DNA synthesis, as well as on extradomain-A fibronectin and keratan sulfate content. Glycosaminoglycan polysulfate stimulated dose-dependent incorporation of [35S]methionine into protein and fibronectin, whereas incorporation of [3H]thymidine into DNA was unaffected. Total fibronectin, extradomain-A fibronectin, and keratan sulfate content were high in chondrocyte cultures treated with glycosaminoglycan polysulfate. In contrast, fibronectin and DNA synthesis, as well as extradomain-A fibronectin and keratan sulfate content were unaffected by diclofenac-Na. S-Adenosyl-methionine decreased dose-dependently the synthesis of fibronectin, as well as the content of fibronectin and keratan sulfate. At the highest concentration of S-adenosyl-methionine tested, findings suggest that cell viability was impaired as assessed by the release of lactate dehydrogenase into the media.
Steinmeyer
J
J
James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Burton-Wurster
N
N
Lust
G
G
D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology; D004285:Dogs / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis / Q000187:drug effects*; D006025:Glycosaminoglycans / Q000494:pharmacology; D007632:Keratan Sulfate / Q000096:biosynthesis*; D012436:S-Adenosylmethionine / Q000494:pharmacology
D005353:Fibronectins; D006025:Glycosaminoglycans; D004008:Diclofenac; C013786:A73025; D012436:S-Adenosylmethionine; D004247:DNA; D007632:Keratan Sulfate