Altern Ther Health Med. 2023 Jul;29(5):410-416.
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.
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.
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.
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.
多聚（ADP-核糖）聚合酶-1（PARP-1）是一种参与 DNA 损伤修复、基因转录、细胞生长、死亡和凋亡的调节酶。在我们的研究中，我们旨在探索 PARP-1 在体外软骨细胞（CH）退变中的动态作用。
我们使用原代 CH 并使用白细胞介素-1β（IL-1β）处理它们，最多 5 天。（IL-1β）诱导退变。同时，我们使用 AG-14361（AG）抑制内源性 PARP-1 表达。细胞存活和胶原 II 表达用于定义 CH 的细胞功能。此外，还测量了其他代谢指标，包括活性氧（ROS）水平、8-羟基-2'-脱氧鸟苷（8-OH-dG）、IL-1β、肿瘤坏死因子-α（TNF-α）和 caspase 3/9 表达。
随着 IL-1β 的处理，CHs 的 PARP1 表达从第 1 天逐渐增加到第 5 天，伴随着细胞存活和胶原 II 表达的减少，ROS、8-OH-dG、IL-1β、TNF-α 和 caspase 3/9 水平的增加。我们在 IL-1β 刺激的第 1 天抑制了 PARP1 表达，发现细胞存活和胶原 II 含量严重破坏，caspase 3/9 表达更高。然而，当我们在 5 天 IL-1β 刺激的第 3 天用 AG 培养 CH 时，细胞存活和胶原 II 表达得到挽救，ROS、8-OH-dG、IL-1β、TNF-α 和 caspase 3/9 下调。
在退变的第 1 天，增加的 PARP-1 在 CHs 中发挥保护作用。然而，从退变的第 3 天到第 5 天，积累的 PARP-1 在 CHs 中呈现出更具破坏性的功能。
