Abstract
Many studies have shown marked changes in syntheses of cartilage matrix macromolecules, matrix metalloproteinases and proinflammatory molecules, including cytokines and chemokines, in cultures of chondrocytes, osteoblasts, synoviocytes and inflammatory cells after addition of hyaluronan to the culture medium, but there are few studies showing the effect of high molecular weight hyaluronan on the synthesis of these proteins or gene expression in joint cartilage in vivo. The purpose of this study was to identify target genes for high molecular weight hyaluronan in OA cartilage in vivo. Iodoacetate was injected into rat joints to develop a rat OA model. Gene expression in articular cartilage of the OA model at knee joints was examined by DNA microarray analysis after intraarticular injections of high molecular weight hyaluronan. High molecular weight hyaluronan enhanced mRNA expression of collagen type IV, IX and XI and adrenomedullin, which were suppressed in the OA model. In contrast, it decreased mRNA expression of several proinflammatory molecules, including phospholipase A2 and toll-like receptor8, which were enhanced in the OA model. These target genes may be involved in the beneficial action of hyaluronan in OA cartilage, and may be useful in the evaluation of the hyaluronan action on OA joints.
