The Effect of Endogenous PARP-1 in Different Phases of IL-1β-Induced Chondrocyte Degeneration
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Objective:
Poly (ADP-ribose) polymerase-1 (PARP-1) is a regulatory enzyme involved in DNA damage repair, gene transcription, cell growth, death and apoptosis. In our study, we aimed to explore the dynamic role of PARP-1 in chondrocyte (CH) degeneration in vitro.
Methods:
We used the primary CHs and treated them with interleukin-1 beta for up to 5 days. (IL-1β) to induce degeneration. Meanwhile, we used AG-14361 (AG) to inhibit endogenous PARP-1 expression. Cell survival and collagen II expression were used to define the cell function of CHs. In addition, other metabolic indicators were measured containing the reactive oxygen species (ROS) level, 8-Hydroxy-2'-deoxyguanosine (8-OH-dG), IL-1β, tumor necrosis factor alpha (TNF-α) and caspase 3/9 expression.
Results:
With IL-1β treatment, the PARP1 expression of CHs was gradually increased from day 1 to day 5, accompanied by a reduction in cell survival and collagen II expression, and an increase in ROS, 8-OH-dG, IL-1β, TNF-α and caspase 3/9 levels. We suppressed PARP1 expression on the first day of IL-1β stimulation and found severe destruction of cell survival and collagen II content with a higher expression of caspase 3/9. However, when we cultured the CHs with AG from day 3 of the 5-day IL-1β stimulation, cell survival and collagen II expression were rescued, and the ROS, 8-OH-dG, IL-1β, TNF-α, and caspase 3/9 were downregulated.
Conclusions:
On day 1 of degeneration, increased PARP-1 played a protective role in CHs. However, from days 3 to 5 of degeneration, the accumulated PARP-1 presented a more destructive function in CHs.
