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bioRxiv · 10.1101/2025.04.15.648880

FGF8 promotes lipid droplet accumulation via the FGFR1/p-p38 axis in chondrocytes

huang, m.·chen, h.·wei, j.·pi, c.·duan, m.·pu, x.·niu, z.·xu, s.·tu, s.·liu, s.·li, j.·zhang, l.·liu, y.·xu, c.·xie, j.
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Abstract

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 aimed to elucidate the role of FGF8 in LDs and explore the underlying biomechanism involved. The results showed that FGF8 promoted 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 confirmed the importance of the FGFR1/p38 axis for LD accumulation in chondrocytes exposed to FGF8. These 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.

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huang, m., chen, h., wei, j., pi, c., duan, m., pu, x., niu, z., xu, s., tu, s., liu, s., li, j., zhang, l., liu, y., xu, c., xie, j.. 2025-04-16. FGF8 promotes lipid droplet accumulation via the FGFR1/p-p38 axis in chondrocytes. https://doi.org/10.1101/2025.04.15.648880

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