FGF7 promotes load-bearing tendon regeneration and suppresses fibrosis

2025-12-27
Nature Communications
Ruifu Lin, Junchao Luo, Hong Zhang, Chunmei Fan, Yue Hu, Ruojin Yan, Zetao Wang, Yang Fei, Chenqi Tang, Tianxi Huang, Tianshun Fang, Weiliang Shen, Sunbin Ling, Hongwei Ouyang, Xiao Chen, Zi Yin

Abstract

Tissue fibrosis is a major cause of organ dysfunction. Preventing fibrosis in tissue pathological condition remains a significant clinical challenge. Here we investigate the role of fibroblast growth factor 7 (FGF7) in mitigating fibrosis and promoting regeneration of load-bearing tendons. Fgf7 knockout mice exhibit impaired motor function and disordered matrix assembly in tendons. Single-cell RNA sequencing reveals an enrichment of a pro-fibrotic cell subpopulation in Fgf7-deficient tendons, which is also predominant in human tendinopathy. Using ProTracer technology, we find that FGF7 deficiency drives proliferating cells toward this pro-fibrotic lineage. Furthermore, we find that FGF7 promotes the tenogenic differentiation of tendon stem/progenitor cells while suppressing their fibrotic differentiation. Importantly, a hydrogel loaded with recombinant FGF7 effectively reduces fibrosis and significantly promotes functional tendon regeneration in vivo. These findings elucidate FGF7’s dual role in driving tenogenesis and inhibiting fibrosis, suggesting a potential therapeutic strategy.