Macrophage pyroptosis promotes synovial fibrosis through the HMGB1/TGF- β1 axis: an in vivo and in vitro study

Pyroptosis-related crosstalk in osteoarthritis: Macrophages, fibroblast-like synoviocytes and chondrocytes

“…Therefore, synovial fluid functions as a medium for the exchange of substances between these cells, facilitating the interaction of decaying cartilage debris, cytokines, and proteases released into the synovial fluid and various cellular components. This subsequent interaction triggers pyroptosis or an inflammatory response, leading to the development of pathological alterations in joint inflammation [ 9 , [66] , [67] , [68] , [69] , [70] ]. During the process of ‘mechanical crosstalk’, CC pyroptosis disrupts the balance between extracellular matrix (ECM) synthesis and catabolism, leading to cartilage breakdown.…”

“…These cells play a crucial role in maintaining intra-articular material homeostasis, modulating inflammatory responses, and participating in intercellular signaling pathways [ 5 , 77 ]. Some studies have shown a close relationship between MC pyroptosis and aseptic chronic inflammation, chronic inflammation, which can result in synovial fibrosis and exacerbation of OA symptoms [ 10 , 70 ]. Zhang et al found that coculture of MC transfected with GSDMD siRNA with FLS downregulates fibrosis markers in the latter, suggesting that inhibiting macrophage pyroptosis could potentially reduce fibrosis in knee OA [ 70 ].…”

“…In vitro studies conducted by Wu et al revealed that the induction of MC pyroptosis resulted in the release of HMGB1, which subsequently led to increased levels of fibrosis markers in FLS. Further analysis demonstrated that inhibiting HMGB1 effectively reduced synovial fibrosis [ 10 ]. Xiao et al observed increased levels of HMGB1 and fibrosis markers in synovial tissues of rats with knee OA, which was attributed to elevated HMGB1 production resulting from FLS pyroptosis [ 82 ].…”

“…The role of cellular pyroptosis in OA has received wide attention in recent years, and the potential mechanisms by which pyroptosis regulates the development of OA have been identified [ 9 , 10 ]. Throughout the progression of OA, pyroptosis can possibly induce pathological alterations within inflamed joints, such as impairments in cartilage integrity, fractures, and synovial tissue inflammation and fibrosis [ [11] , [12] , [13] , [14] ].…”