title: Protective effect of hyaluronic acid on interleukin-1-induced deregulation of beta1-integrin and insulin-like growth factor-I receptor signaling and collagen biosynthesis in cultured human chondrocytes.
abstract: The mechanism of protective action of hyaluronic acid (HA) on collagen metabolism disturbances in tissues during inflammation is not known. Insulin-like growth factor-I (IGF-I) receptor and beta1-integrin receptor signaling plays an important role in the regulation of collagen biosynthesis at both transcriptional and post-transcriptional levels. The present study was undertaken to evaluate the effect of IL-1beta (inductor of experimental inflammation) on the signaling pathways as well as on collagen biosynthesis, gelatinases and prolidase activity in cultured human chondrocytes and the effect of HA on these processes. It was found that IL-1beta-dependent inhibition of collagen biosynthesis was accompanied by increase in beta1-integrin receptor, NF-kB expressions, and increase in phosphorylation of FAK, that resulted in stimulation of metalloproteinase MMP-2 and MMP-9 activities, but not prolidase activity and expression. Simultaneously, decrease in expression of IGF-I receptor and phosphorylation of Akt and p38 were found. All those processes were counteracted by HA. This suggests that cross talk between beta1-integrin and IGF-I receptors is disturbed by IL-1beta, and HA recovers their proper signaling in cultured chondrocytes. We propose that IGF-I receptor and beta1-integrin signaling may play an important role in protective effect of hyaluronic acid on interleukin-1-induced inhibition of collagen biosynthesis in cultured human chondrocytes.
authors: Department of Medicinal Chemistry, Medical University in Białystok, Kilińskiego 1, 15-089 Bialystok, Poland.
authors: Ewa
authors: E
authors: Karna
authors: Wojciech
authors: W
authors: Miltyk
authors: Arkadiusz
authors: A
authors: Surazyński
authors: Jerzy A
authors: JA
authors: Pałka
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis*; D004150:Dipeptidases / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D019012:Integrin beta1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014316:Tritium
chemical_list: D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D007375:Interleukin-1; D016328:NF-kappa B; D020011:Protective Agents; C098946:hyaluronan-mediated motility receptor; D014316:Tritium; D005780:Gelatin; D006820:Hyaluronic Acid; D003094:Collagen; D011392:Proline; D011494:Protein Kinases; D017526:Receptor, IGF Type 1; D004150:Dipeptidases; C022449:proline dipeptidase