Fibroblast growth factor 7 protects osteoblasts against oxidative damage through targeting mitochondria

• Published in: The FASEB journal 2024-03, Vol.38 (5), p.e23524-n/a
• Main Authors: Liu, Xiaoyu, Hu, Xuchen, Niu, Chenguang, Yang, Yueyi, Huang, Zhengwei, Xie, Jing
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; FGF7; Fibroblast Growth Factor 7; Mice; Mitochondria; Osteoblasts; Osteogenesis; Oxidative Stress; ROS
• ISSN: 0892-6638; 1530-6860
• 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 (H2O2). We first provided the evidence that the endogenous FGF7 was significantly increased in osteoblasts in response to the increased H2O2 levels. Recombined FGF7 demonstrated a remarkable capacity to resist the detrimental effects of H2O2‐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 H2O2‐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. FGF7 protects against H2O2‐induced osteoblast dysfunction, improving cell viability, reducing apoptosis, and enhancing osteogenic differentiation. This effect is attributed to FGF7's ability to maintain redox balance and mitochondrial homeostasis. Additionally, FGF7 activates the p38/MAPK signaling pathway and inhibits the JNK/MAPK signaling pathway under oxidative stress.