Protective effect of hyaluronic acid on interleukin-1-induced deregulation of β₁-integrin and insulin-like growth factor-I receptor signaling and collagen biosynthesis in cultured human chondrocytes

• Published in: Molecular and cellular biochemistry 2008, Vol.308 (1-2), p.57-64
• Main Authors: Karna, Ewa, Miltyk, Wojciech, Surażyński, Arkadiusz, Pałka, Jerzy A
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Cardiology; Collagen metabolism; FAK; hyaluronic acid; IGF-I receptor; interleukin-1; Life Sciences; MAPK; Medical Biochemistry; Oncology; Prolidase; β₁-integrin, Chondrocyte
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-007-9612-5

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 β1-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-1β (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-1β-dependent inhibition of collagen biosynthesis was accompanied by increase in β1-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 β1-integrin and IGF-I receptors is disturbed by IL-1β, and HA recovers their proper signaling in cultured chondrocytes. We propose that IGF-I receptor and β1-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.