Oxidative stress is known to inhibit osteogenesis and PKD1 is implicated in bone remodeling and skeletogenesis. In the present study, we explored the role of PKD1 in osteogenesis under oxidative stress. H₂O₂ was used to induce oxidative stress in rat bone marrow (BM)-mesenchymal stem cells (MSCs) during osteoblast differentiation. Alkaline phosphatase (ALP) activity, calcium deposits, and the RUNX2 marker were assayed to determine osteogenic differentiation. The correlation of PKD1, Sirt1, c-MYC, and TAZ was further confirmed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. We found that H₂O₂ induced the downregulation of PKD1 expression and the upregulation of c-MYC, and Sirt1 was accompanied by decreasing cell viability in BM-MSCs. During osteogenic differentiation, the expression of PKD1 was upregulated significantly whereas Sirt1 tended to be upregulated mildly under normal conditions. Both PKD1 and Sirt1 were upregulated upon oxidative stress. The positive correlation of PKD1 expression with osteogenic differentiation under normal conditions might be hindered by oxidative stress and PKD1 could interact with TAZ under oxidative stress to regulate osteogenic differentiation. Our results suggest that PKD1 may alleviate oxidative stress-inhibited osteogenesis of rat BM-MSCs through TAZ activation.

中文翻译：

---

PKD1通过TAZ激活减轻大鼠骨髓间充质干细胞的氧化应激抑制成骨

已知氧化应激抑制成骨，PKD1 与骨重塑和骨骼形成有关。在本研究中，我们探讨了 PKD1 在氧化应激下成骨中的作用。H ₂ O ₂用于在成骨细胞分化过程中诱导大鼠骨髓 (BM)-间充质干细胞 (MSCs) 中的氧化应激。测定碱性磷酸酶 (ALP) 活性、钙沉积物和 RUNX2 标志物以确定成骨分化。PKD1、Sirt1、c-MYC 和 TAZ 的相关性通过染色质免疫沉淀 (ChIP) 和双荧光素酶报告基因分析得到进一步证实。我们发现 H ₂ O ₂诱导PKD1表达的下调和c-MYC的上调，并且Sirt1伴随着BM-MSC中细胞活力的降低。在成骨分化过程中，PKD1的表达显着上调，而Sirt1在正常条件下倾向于轻度上调。PKD1 和 Sirt1 在氧化应激时均上调。正常条件下PKD1表达与成骨分化的正相关可能受到氧化应激的阻碍，PKD1可以与氧化应激下的TAZ相互作用以调节成骨分化。我们的研究结果表明，PKD1 可通过 TAZ 激活减轻氧化应激抑制的大鼠 BM-MSCs 的成骨。