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 inflamma- tion 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-yl）-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 metalloprotei- nases-1 （TIMP-1） were determined by real-time reverse transcriptase-polymerase chain reaction and western blot analysis, respectively. The expression and phosphorylation of NF-κB 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, resultlng in NF-κB p65 nuclear translocation and phos-phorylation 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-κB pathway. These data suggested that PARP-1 inhibition prevents IL-1β-induced inflammation response at least partly by inhibiting the IL-1R/NF-κB signaling pathway in human articular chondrocytes. Moreover, PARP-1 inhibition reduced MMPs expression and increased TIMP-1 expression, suggesting that PARP-1 inhibitiQn 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.