Disease-Modifying Effects of Glucosamine HCl Involving Regulation of Metalloproteinases and Chemokines Activated by Interleukin-1β in Human Primary Synovial Fibroblasts

The purpose of this study was to investigate the possible involvement of synovium in cartilage destruction in osteoarthritis (OA) patients. Using human primary synovial fibroblasts (HPSFs), we examined the effects of glucosamine (GLN) on the regulation of the expression of matrix metalloproteinases (MMP-1, -2, and -13) and chemokines (IL-8, MCP-1, and RANTES) as well as the involvement of MAPK signal pathways (JNK, ERK, and p-38) and the transcription factor of NF-kappa B on the present or absence of interleukin (IL)-1 beta. Our experiments showed that protein production and mRNA expression of MMP-1, MMP-3, IL-8, MCP-1. Our experiments showed that protein protein and mRNA expressions of MMP-1, MMP-3, IL-8, MCP-1, and RANTES were downregulated by treatment with glucosamine in HPSFs. The further showed that GLN could inhibit I kappa B alpha phosphorylation and I kappa B alpha degradation leading to inhibition of the translocation of NF-kappa B to nuclei. However, GLN upregulated MAPKs pathways in HPSFs cells with or without IL-1 beta. The results suggest that the inhibition of MMP-1, and -13 expressions as well as IL-8, MCP-1, and RANTES productions by GLN might mediate suppression of NF-kappa B signal pathways, and HPSFs seem to have a potential functions as an alternative source of MMPs and chemokines for inducing the degradation of cartilage in OA. J. Cell. Biochem. 104:38-50, 2008. (C) 2007 Wiley-Liss, Inc.