Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
FASEB J. 2024 Mar 15;38(5):e23524. doi: 10.1096/fj.202301650RR.
The pathophysiology of osteoporosis is significantly influenced by the impaired functioning of osteoblasts, which is particularly caused by oxidative stress. Nevertheless, the underlying mechanisms responsible for this phenomenon are still not well understood. The objective of this study was to elucidate the impact of fibroblast growth factor 7 (FGF7) on the behavior of osteoblasts under conditions of oxidative stress. The osteoblast-like MC3T3 cells were pretreated with recombinant FGF7 in the presence of oxidative stress induced by hydrogen peroxide (H O ). We first provided the evidence that the endogenous FGF7 was significantly increased in osteoblasts in response to the increased H O levels. Recombined FGF7 demonstrated a remarkable capacity to resist the detrimental effects of H O -induced oxidative stress, including the increase in cell apoptosis, decrease in osteoblast viability, and impairment in osteogenic differentiation capacity, on osteoblasts. Furthermore, we extensively explored the mechanism underlying these protective effects and discovered a remarkable modulation of reactive oxygen species (ROS) homeostasis in H O -treated cells following the pronounced expression of FGF7, which significantly differed from the control group. Additionally, we observed that FGF7 exerted partial preservation on both the morphology and function of mitochondria when exposed to oxidative stress conditions. Furthermore, FGF7 exhibited the ability to enhance the activation of the p38/MAPK signaling pathway while concurrently suppressing the JNK/MAPK signaling pathway in response to oxidative stress. These results underscore the promising role and underlying mechanisms of FGF7 in preserving osteoblast homeostasis in the face of oxidative stress.
骨质疏松症的病理生理学受到成骨细胞功能障碍的显著影响，特别是由氧化应激引起的。然而，导致这种现象的潜在机制仍未得到很好的理解。本研究的目的是阐明成纤维细胞生长因子 7（FGF7）在氧化应激条件下对成骨细胞行为的影响。成骨样 MC3T3 细胞先用过氧化氢（H2O2）诱导氧化应激，然后用重组 FGF7 预处理。我们首先提供证据表明，成骨细胞中内源性 FGF7 随着 H2O2 水平的增加而显著增加。重组 FGF7 表现出显著的抵抗 H2O2 诱导的氧化应激有害影响的能力，包括增加细胞凋亡、降低成骨细胞活力和损害成骨分化能力。此外，我们广泛探讨了这些保护作用的机制，并发现 FGF7 在 H2O2 处理的细胞中显著表达后，对活性氧（ROS）稳态有明显的调节作用，这与对照组有明显的不同。此外，我们观察到 FGF7 在暴露于氧化应激条件下对线粒体的形态和功能有部分保护作用。此外，FGF7 能够增强 p38/MAPK 信号通路的激活，同时抑制 JNK/MAPK 信号通路的激活，以应对氧化应激。这些结果强调了 FGF7 在维持氧化应激下成骨细胞内稳态方面的有希望的作用和潜在机制。
