Involvement of NF-κB/NLRP3 axis in the progression of aseptic loosening of total joint arthroplasties: a review of molecular mechanisms.

Particulate wear debris can trigger pro-inflammatory bone resorption and result in aseptic loosening. This complication remains major postoperative discomforts and complications for patients who underwent total joint arthroplasty. Recent studies have indicated that wear debris-induced aseptic loosening is associated with the overproduction of pro-inflammatory cytokines. The activation of osteoclasts as a result of inflammatory responses is associated with osteolysis. Moreover, stimulation of inflammatory signaling pathways such as the NF-κB/NLRP3 axis results in the production of pro-inflammatory cytokines. In this review, we first summarized the potential inflammatory mechanisms of wear particle-induced peri-implant osteolysis. Then, the therapeutic approaches, e.g., biological inhibitors, herbal products, and stem cells or their derivatives, with the ability to suppress the inflammatory responses, mainly NF-κB/NLRP3 signaling pathways, were discussed. Based on the results, activation of macrophages following inflammatory stimuli, overproduction of pro-inflammatory cytokines, and subsequent differentiation of osteoclasts in the presence of wear particles lead to bone resorption. The activation of NF-κB/NLRP3 signaling pathways within the macrophages stimulates the production of pro-inflammatory cytokines, e.g., IL-1β, IL-6, and TNF-α. According to in vitro and in vivo studies, novel therapeutics significantly promoted osteogenesis, suppressed osteoclastogenesis, and diminished particle-mediated bone resorption. Conclusively, these findings offer that suppressing pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome represents a novel approach to attenuate wear-particle-related osteolytic diseases.