Disease‐modifying effects of Glucosamine HCl involving regulation of metalloproteinases and chemokines activated by interleukin‐1β in human primary synovial fibroblasts

Abstract

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-kappaB on the present or absence of interleukin (IL)-1beta. Our experiments showed that protein production and mRNA expressions of MMP-1, MMP-3, MMP-13, IL-8, MCP-1, and RANTES were downregulated by treatment with glucosamine in HPSFs. The results further showed that GLN could inhibit IkappaBalpha phosphorylation and IkappaBalpha degradation leading to inhibition of the translocation of NF-kappaB to nuclei. However, GLN upregulated MAPKs pathways in HPSFs cells with or without IL-1beta. The results suggest that the inhibition of MMP-1, -3, and -13 expressions as well as IL-8, MCP-1, and RANTES productions by GLN might mediate suppression of NF-kappaB 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.

The Effect of Glucosamine Sulfate on the Proliferative Potential and Glycosaminoglycan Synthesis of Nucleus Pulposus Intervertebral Disc Cells

“…35 -38 Our observation about p38 MAPK activation by a 2-hour treatment with glucosamine sulfate alone that is enhanced by salt addition is in accordance with the reported induction of p38 MAPK phosphorylation in human primary synovial fi broblasts by glucosamine treatment, which is further promoted by IL-1 β . 39 Furthermore, we describe a decrease in the ERK and JNK basal and hyperosmolalityinduced phosphorylation levels stimulated by the highest concentration of the compound, when existing literature concerning these molecules' behavior in the presence of glucosamine is controversial. 2 , 4 , 12 , 32 , 39 -43 However, the phosphorylation pattern of the 3 members of the MAPK superfamily after exposure to 10 mM of glucosamine sulfate in our study could be easily justifi ed by the increased osmotic pressure measured under the particular experimental conditions.…”

Protective effects of butanol fraction from Betula Platyphyla var. japonica on cartilage alterations in a rabbit collagenase-induced osteoarthritis

“…Recent research demonstrated that MMP-1 was involved in OA development in rabbit ACLT model and the amount of its expression was related with the degree of cartilage degradation . Glucosamine have a potential functions as an alternative source of MMP-1 and MMP-3 for inducing the degradation of cartilage in OA (Lu et al, 2008). Hyaluronic acid and glucosamine sulfates all can decrease the level of MMP-3 and the ratio of MMP-3/TIMP-1 in the synovial fluid in knee joints with OA (Xu et al, 2008).…”

Cordycepin prevented IL-β-induced expression of inflammatory mediators in human osteoarthritis chondrocytes

“…We speculated that the differences maybe attribute to the different types of cells. In RASFs, AP-1 is an essential component for MMP-1 synthesis, and cooperation between mitogen-activated protein kinase (MAPK) and NF-κB signalling pathways is necessary for IL-1β-induced synthesis of MMP-1 [35]. Ren et al [36] found that cordycepin inhibited NF-κB signaling by suppressing NF-κB and IκB-α activity in Fig.…”