Alterations in articular chondrocyte growth and proteoglycan synthesis due to prostanoid precursors.
The effects of the prostaglandin precursors, dihomo-gamma-linolenic acid and arachidonic acid, on chondrocyte proliferation, proteoglycan synthesis and morphological structure were studied using lapine articular chondrocytes in vitro. Neither substance exerted a cytotoxic effect on chondrocytes. Dihomo-gamma-linolenic acid caused a dose-dependent inhibition of chondrocyte proliferation (8% and 35% reduction at 10 and 100 mumol/l respectively) (P less than 0.01), whereas arachidonic acid failed to cause any significant alteration: 10 mumol/l of dihomo-gamma-linolenic acid stimulated proteoglycan synthesis by 14% (P less than 0.01), whilst 100 mumol/l elicited a reduction of 14% (P less than 0.01); 100 mumol/l of arachidonic acid also caused a statistically significant inhibition (31%) (P less than 0.001) of 35SO4 incorporation into proteoglycans. The inhibitory effects on proteoglycan synthesis may be mediated by intracellularly synthesized prostaglandins, which are known to exert this effect. This may also help explain the susceptibility of articular cartilage to damage with increasing age, as arachidonic acid is found in increasing concentrations in the superficial layers of articular cartilage.
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000032:analysis / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*; D011817:Rabbits
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D011509:Proteoglycans; D004247:DNA; D015126:8,11,14-Eicosatrienoic Acid