Mechanical stretch promotes the neutrophil recruitment potential of fibroblasts through the Piezo/NFAT1/LIF axis

Abstract

The entheses are the sites where tendons or ligaments insert into osseous structures and play a crucial role in transmitting mechanical stress from muscles to bones. Under excessive mechanical loads, the entheses may sustain inflammation, leading to isolated enthesitis. However, the specific mechanisms through which enthesitis occurs have not yet been fully elucidated. In our study, we discovered that mechanical stress is a critical factor that drives fibroblasts to recruit neutrophils through the secretion of leukemia inhibitory factor (LIF). Further research revealed that fibroblasts convert mechanical stress, a physical signal, into a chemical signal through the Piezo mechanosensitive ion channel, subsequently activating the transcription factor NFAT1 and upregulating LIF expression. This study not only helps elucidate the mechanisms underlying the development of enthesitis but also offers potential insights into the clinical management and treatment of patients with enthesitis.