Double-stranded RNA released from damaged articular chondrocytes promotes cartilage degeneration via Toll-like receptor 3-interleukin-33 pathway.

ABSTRACT: Pattern recognition receptors (PRRs), including Toll-like receptor 3 (TLR3), are involved in arthritic responses; however, whether interleukin-33 (IL-33) is involved in TLR3-mediated cartilage degeneration is unknown. Here, we found that IL-33 was abundantly increased in chondrocytes of osteoarthritis, especially the chondrocytes of weight-bearing cartilage. Furthermore, double-stranded RNA (dsRNA) released from damaged articular chondrocytes induced by mechanical stretching upregulated IL-33 expression to a greater degree than IL-1? and tumor necrosis factor-?. dsRNA induced IL-33 expression via the TLR3-p38 mitogen-activated protein kinase-nuclear factor-?B (NF-?B) pathway. In addition, formation of the p65 and peroxisome proliferator-activated receptor-? transcriptional complex was required for dsRNA-induced IL-33 expression. IL-33, in turn, acted on chondrocytes to induce matrix metalloproteinase-1/13 and inhibit type II collagen expression. These findings reveal that dsRNA released from damaged articular chondrocytes promotes cartilage degeneration via the TLR3-IL-33 pathway.

SUBMITTER: Li C 

PROVIDER: S-EPMC5775407 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature