Huang Minglei, Chen Haoran, Wei Jieya, Pi Caixia, Duan Mengmeng, Pu Xiaohua, Niu Zhixing, Xu Siqun, Tu Shasha, Liu Sijun, Li Jiazhou, Zhang Li, Liu Yang, Chen Hao, Xu Chunming, Xie Jing
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China.
Acta Biochim Biophys Sin (Shanghai). 2025 May 15. doi: 10.3724/abbs.2025075.
Chondrocytes store lipids in the form of lipid droplets (LDs) and maintain cartilage lipid metabolic homeostasis by consuming or regenerating LDs. This modulation is largely mediated by a series of biochemical factors. Fibroblast growth factor 8 (FGF8) is one of the most important factors involved in the proliferation, differentiation, and migration of chondrocytes and has attracted increasing attention in the physiology and pathology of cartilage. However, the effect of FGF8 on LD accumulation in chondrocytes remains unclear. This study aims to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results reveal that FGF8 promotes LD accumulation in chondrocytes by upregulating perilipin1 (Plin1) expression. FGF8 activates the cytoplasmic p-p38 signaling pathway via fibroblast growth factor receptor 1 (FGFR1) to increase LD accumulation in chondrocytes. Subsequent experiments with siRNAs and specific inhibitors further confirm the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. The results increase our understanding of the role of FGF8 in the lipid metabolic homeostasis of chondrocytes and provide insights into the physiology and pathology of cartilage.
软骨细胞以脂滴（LDs）的形式储存脂质，并通过消耗或再生脂滴来维持软骨脂质代谢稳态。这种调节主要由一系列生化因子介导。成纤维细胞生长因子8（FGF8）是参与软骨细胞增殖、分化和迁移的最重要因子之一，在软骨的生理学和病理学方面受到越来越多的关注。然而，FGF8对软骨细胞中脂滴积累的影响仍不清楚。本研究旨在阐明FGF8在脂滴中的作用，并探索其潜在的生物力学机制。结果表明，FGF8通过上调脂滴包被蛋白1（Plin1）的表达促进软骨细胞中脂滴的积累。FGF8通过成纤维细胞生长因子受体1（FGFR1）激活细胞质中的p-p38信号通路，以增加软骨细胞中脂滴的积累。随后用小干扰RNA（siRNAs）和特异性抑制剂进行的实验进一步证实了FGFR1/p38轴对于暴露于FGF8的软骨细胞中脂滴积累的重要性。这些结果增进了我们对FGF8在软骨细胞脂质代谢稳态中作用的理解，并为软骨的生理学和病理学提供了见解。
