Sensory nerves protect against tendon degeneration via FGF1/FGFR signaling

Single-cell RNA sequencing (scRNA-seq) of tendinous tissue identified defective tenocyte differentiation and altered macrophage migration and polarization with surgical denervation. Retrograde neuronal tracing in combination with scRNA-seq of corresponding dorsal root ganglia (DRG) tissues identified the profile of tendon-specific innervation, which included CGRP+ nociceptors among other neuron types. Finally, neuron-tendon interaction analyses implicated neuron-derived fibroblast growth factor 1 (FGF1) as a potent regulator of tendon repair, a finding experimental confirmed with tendon organ culture.

Collectively, our findings demonstrate that peripheral afferent neural networks induce a protective effect in chronic tendinopathy by secreting FGF1, and that targeting this pathway may offer therapeutic strategies to enhance tendon repair.