Abstract
Rheumatoid arthritis (RA), a common autoimmune disorder, is associated with a chronic inflammatory response and unbalanced bone metabolism within the articular microenvironment. Adiponectin, an adipokine secreted by adipocytes, is involved in multiple functions, including lipid metabolism and pro-inflammatory activity. However, the mechanism of adiponectin performance within arthritic inflammation remains unclear. In this study, we observed the effect of adiponectin on the expression of oncostatin M (OSM), a pro-inflammatory cytokine, in human osteoblastic cells. Pretreatment of cells with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB reduced the adiponectin-induced OSM expression in osteoblasts. Stimulation of the cells with adiponectin increased phosphorylation of PI3K, Akt, and p65. Adiponectin treatment of osteoblasts increased OSM-luciferase activity and p65 binding to NF-κB on the OSM promoter. Our results indicate that adiponectin increased OSM expression via the PI3K, Akt, and NF-κB signaling pathways in osteoblastic cells, suggesting that adiponectin is a novel target for arthritis treatment.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disorder with unknown etiology
We further investigated whether nuclear factor (NF)-κB activation is involved in adiponectin-mediated oncostatin M (OSM) expression by using the NF-κB inhibitors pyrrolidine dithiocarbamate (PDTC) and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) or p65 Small-interfering RNAs (siRNAs)
Previous studies have demonstrated the impact of inflammation in osteoclasts, an increasing number of recent studies have focused on the role of osteoblasts in RA pathogenesis [11,19]
Summary
The most typical characterization of RA includes inflammatory synovium and bone destruction because of abnormal immune responses and an accumulation of pro-inflammatory cytokines in the joints [1]. Osteoblast-mediated bone formation can repair bone erosion, but the effect of pro-inflammatory cytokines on osteoblast function remains unclear. It was shown that in addition to their role in metabolic functions, adipocytes surrounding the RA joints secrete adipokines that may regulate inflammatory and immune processes [3]. Adiponectin, an adipokine secreted by adipocytes, is associated with metabolic syndromes and pro-inflammatory activity. Adiponectin has been proven to play a role in the function of RA synovial fibroblasts, and to exert different actions in osteoblasts as well. The mechanisms accounting for the adiponectin-mediated actions in osteoblasts have not been determined
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