Poly(ADP-ribose) polymerase 1 inhibition prevents interleukin-1β-induced inflammation in human osteoarthritic chondrocytes

Osteoarthritis (OA) is an age-related joint disease that is characterized by the degeneration of articular chondrocytes. Nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is associated with inflammation response. We investigated the role of PARP-1 in interleukin-1β (IL-1β)-stimulated human articular chondrocytes and its underlying mechanism. Cell viability and apoptosis were evaluated by using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay and flow cytometry, respectively. Tumor necrosis factor-α (TNF-α) level was measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of PARP-1, IL-1 receptor (IL-1R), inducible nitric oxide synthase (iNOS), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were determined by real-time reverse transcriptase-polymerase chain reaction and western blot analysis, respectively. The expression and phosphorylation of NF-кB p65 were measured by western blot analysis. Results showed that stimulation of chondrocytes with IL-1β caused a significant up-regulation of PARP-1 and IL-1R, resulting in NF-кB p65 nuclear translocation and phosphorylation associated with an increase of TNF-α secretion and iNOS expression. PARP-1 was inhibited by siRNA transfection. Results showed that PARP-1 inhibition suppressed IL-1β-induced reduction of cell viability and up-regulation of cell apoptosis, with a reduced IL-1R expression. PARP-1 inhibition also effectively reversed IL-1β-induced inflammatory response through inhibiting the IL-1R/NF-кB pathway. These data suggested that PARP-1 inhibition prevents IL-1β-induced inflammation response at least partly by inhibiting the IL-1R/NF-кB signaling pathway in human articular chondrocytes. Moreover, PARP-1 inhibition reduced MMPs expression and increased TIMP-1 expression, suggesting that PARP-1 inhibition could suppress cartilage destruction by modulating the balance between MMPs and TIMP-1. Inhibition of PARP-1 might be useful in the treatment of OA.