Focus on necroptosis: its role in the pathogenesis and therapeutic potential of osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by the progressive deterioration of joint structures. This deterioration results in pain and functional impairment and is a significant contributor to disability and economic strain. Necroptosis represents a crucial form of programmed cell death (PCD) that operates independently of caspases; it is governed by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). Necroptosis plays a pivotal role in various inflammatory, infectious, and degenerative pathologies. Recent research studies have highlighted the significant involvement of necroptosis in the advancement of OA. This article delineates the processes underlying the initiation and execution of necroptosis and explores its potential mechanisms within OA. It emphasizes the interplay between necroptosis and oxidative stress, inflammatory responses, extracellular matrix degradation, and cartilage repair and regeneration. Ultimately, this review assesses the existing evidence regarding the potential of targeting necroptosis as a therapeutic avenue for OA, positing that inhibition of the necroptosis pathway may emerge as a novel strategy to mitigate symptoms of OA and impede the progression of joint degeneration.