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Periprosthetic osteolysis (PPO) along with aseptic loosening (AL) caused by wear particles after artificial joint replacement is the key factor in surgical failure and subsequent revision surgery, however, the precise molecular mechanism underlying PPO remains unclear. Aseptic inflammation triggered by metal particles, resulting in the imbalance between bone formation by osteoblasts and bone resorption by osteoclasts may be the decisive factor. Pyroptosis is a new pro-inflammatory pattern of regulated cell death (RCD), mainly mediated by gasdermins (GSDMs) family, among which GSDMD is the best characterized. Recent evidence indicates that activation of NLRP3 inflammasomes and pyroptosis play a pivotal role in the pathological process of PPO. Here, we review the pathological process of PPO, the molecular mechanism of pyroptosis and the interventions to inhibit the inflammation and pyroptosis of different cells during the PPO. Conclusively, this review provides theoretical support for the search for new strategies and new targets for the treatment of PPO by inhibiting pyroptosis and inflammation. [ABSTRACT FROM AUTHOR]

[Display omitted] • CoP-challenged macrophages can accelerate osteoclastogenesis. • CoPs result in macrophages pyroptosis and release of inflammatory cytokines. • CoPs stimulation promotes ROS accumulation and subsequently activates NLRP3. • High-concentration CoPs suppress mitophagy, further enhancing macrophages pyroptosis. • By promoting mitophagy and inhibiting NLRP3, CoP-induced osteolysis can be delayed. Wear particles derived from implant surfaces are the important factors causing periprosthetic osteolysis (PPO), which is the main reason for total joint revision. To date, the specific pathogenesis of PPO remains largely unknown, and developing new therapeutic strategies is urgently necessary. Our study indicated the most clinically common cobalt- chromium-molybdenum (CoCrMo) wear particles (CoPs) activated macrophages and further accelerated osteoclastogenesis. Subsequently, we put emphasis on the pathologic change in macrophages after CoPs stimulation. Meaningfully, high-concentration CoPs induced reactive oxygen species (ROS) accumulation in macrophages and activated NOD-like receptor pyrin domain-containing 3 (NLRP3)-dependent pyroptosis, promoting the release of cytokines such as IL-18, IL-1β and HMGB1, and subsequent formation of extracellular inflammatory microenvironment, which is crucial for osteoclastogenesis. More interestingly, transmission electron microscopy and flow cytometry results revealed that there were accumulation of endamaged mitochondria in high-concentration CoP-challenged macrophages, which accelerated intracellular ROS accumulation and mediated NLRP3-dependent pyroptosis. Mechanismly, high-concentration CoPs induced macrophage mitophagy impairment and the loss of mitochondrial membrane potential via inhibiting PINK1/Parkin signalling pathway. Furthermore, by subcutaneous injection of salidroside and/or CY-09 in situ significantly delayed CoP-induced mice calvaria osteolysis. Collectively, this study demonstrates a novel mechanism underlying the pathogenesis of PPO and provides a potential therapy avenue. [ABSTRACT FROM AUTHOR]

• EsA attenuates inflammation and catabolism of chondrocytes. • EsA restrains RANKL-induced osteoclast formation. • Treatment with EsA suppresses NF-κB and MAPK signalling pathway activation in vitro. • EsA protects OA cartilage in vivo and may be a novel therapeutic target. Osteoarthritis is a relatively common disorder of articular deterioration related to cartilage damage, subchondral bone remodelling, inflammation and metabolism. Agents that can inhibit cartilage degradation and osteoclastogenesis are required for the prevention and treatment of osteoarthritis. Esculentoside A, the highest concentration triterpene saponin isolated from the root of Phytolacca esculenta, has commonly been used for the treatment of chronic bronchitis. However, the role esculentoside A plays in ameliorating osteoarthritis has not been reported. We found that esculentoside A suppresses the expression of IL-1β-induced inflammatory and metabolic factors (IL-6, IL-8, TNF-α, MMP2, MMP3 and MMP13). In addition, esculentoside A restrains osteoclast formation by inhibiting the marker gene expression of NFATc1 and c-Fos. Our results indicate that esculentoside A markedly suppresses IL-1β-induced NF-κB and MAPK signalling pathway activation in chondrocytes, and inhibits RANKL-induced osteoclast precursor generation. Finally, treatment with esculentoside A inhibits the progressive cartilage degeneration and osteoclastogenesis in osteoarthritis mouse models. In summary, these results demonstrate that esculentoside A could be a latent therapeutic reagent for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]