title: Hyaluronic acid counteracts interleukin-1-induced inhibition of collagen biosynthesis in cultured human chondrocytes.
abstract: Although, hyaluronic acid (HA) is used in the treatment of osteoarthritis for 30 years, the mechanism of its protective action on collagen metabolism disturbances in tissues during inflammation is not known. Therefore, the present study was undertaken to evaluate the mechanism of IL-1beta action (inductor of experimental inflammation) on deregulation of collagen biosynthesis in cultured human chondrocytes and the effect of HA on the process. It has been found that IL-1beta strongly induced inhibition of collagen biosynthesis, while HA counteracted the process. The mechanism of this phenomenon was found at both transcriptional and post-transcriptional level. IL-1 was found to down regulate the expression of mRNA for type II collagen and to inhibit prolidase activity, an enzyme that plays an important role in collagen biosynthesis at post-translational level. HA was shown to counteract the IL-1beta-dependent inhibition of both processes. During experimental inflammation of chondrocytes cultured in 0.1% FBS there was no differences in the expression of beta(1)-integrin independently of cell number and the presence of HA in growth medium. In chondrocytes cultured in 5% FBS, IL-1beta up-regulated the expression of beta(1)-integrin receptor while HA abolished the effect. The data suggest that HA-dependent up-regulation of collagen biosynthesis in IL-1beta-treated chondrocytes may involve stimulation of prolidase activity in serum "starved" cells and may also originate at the transcriptional level in the cells cultured in standard conditions.
authors.affiliation: Department of Medicinal Chemistry, Medical University in Białystok, Kilińskiego 1, Białystok, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Karna
authors.forename: W
authors.initials: W
authors.lastname: Miltyk
authors.forename: J A
authors.initials: JA
authors.lastname: Pałka
authors.forename: K
authors.initials: K
authors.lastname: Jarzabek
authors.forename: S
authors.initials: S
authors.lastname: Wołczyński
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000096:biosynthesis*; D004150:Dipeptidases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D019012:Integrin beta1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D046509:Tissue Culture Techniques
chemical_list: D024043:Collagen Type II; D019012:Integrin beta1; D007375:Interleukin-1; D012333:RNA, Messenger; D006820:Hyaluronic Acid; D004150:Dipeptidases; C022449:proline dipeptidase