The Role of Piezo 1 in the Study of Intervertebral Disc Degeneration: Phenotype, Mechanism and Treatment

BACKGROUND: Intervertebral disc degeneration (IVDD), a prevalent spinal disorder, is closely associated with abnormal mechanical stress. The nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP) collectively respond to mechanical loading. The mechanosensitive Piezo 1 ion channel senses mechanical stress changes and converts the mechanical signals into chemical signals, and serves a pivotal role in IVDD pathogenesis. OBJECTIVE: This review summarizes the regional effects of Piezo 1 on mechanical stress-induced IVDD and evaluates therapeutic strategies targeting Piezo 1 to maintain disc homeostasis. METHODS: A systematic search of preclinical and clinical studies was conducted to delineate Piezo 1's phenotypic impacts, mechanistic pathways, and therapeutic potential in NP, AF, and CEP. RESULTS: /Calpain2/Caspase-3 signaling pathway. Therapeutically, targeting Piezo 1 has demonstrated significant preclinical potential, including attenuating pathological alterations via pharmacological inhibition, selectively suppressing degenerative cascades through genetic/RNAi approaches, and modulating channel activity by nutritionally regulating membrane lipids. CONCLUSION: Piezo 1 serves as a critical mechanotransducer in IVDD, exhibiting region-specific effects on disc pathophysiology. Targeting Piezo 1 signaling not only offers mechanistic insights but also holds translational potential as a therapeutic strategy to improve IVDD, meriting further exploration in preclinical and clinical contexts.