[Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].

Steroid-associated necrosis of the femoral head (SANFH) is a refractory osteoarticular disease induced by glucocorticoids, characterized by a complex pathogenesis and limited clinical treatment options. Recent studies have demonstrated that RNA-binding proteins (RBPs) play crucial roles in post-transcriptional regulation, cell signal transduction, and metabolic homeostasis through liquid-liquid phase separation (LLPS). In the pathogenesis of SANFH, RBPs participate in the regulation of key processes involved in bone metabolism via LLPS and may represent potential therapeutic targets. The phase-separation behavior of RBPs can be dynamically regulated by factors such as domain characteristics, RNA-binding status, and the adenosine triphosphate (ATP) microenvironment. These regulatory mechanisms subsequently influence DNA damage repair, ferroptosis, exosome biogenesis, the transforming growth factor-beta (TGF-β)/Sma- and Mad-related protein 7 (Smad7) signaling pathway, inflammasome activation, and m6A modification, all of which are closely associated with the initiation and progression of SANFH. Targeted regulation of RBP phase separation may provide a promising strategy to restore bone metabolism homeostasis, inhibit cell death, and alleviate inflammatory responses through multiple mechanisms. By integrating the emerging cell-biological mechanism of RBP phase separation with the multistage and multipathway pathological progression of SANFH, a novel mechanistic framework is proposed, offering new perspectives for the prevention and treatment of SANFH. Further studies are warranted to elucidate the precise roles of RBP phase separation in SANFH and to explore phase separation-based precision therapeutic strategies.