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• W2085294880 startingPage "35" @default.
• W2085294880 abstract "In osteoarthritis (OA), chronic, low-grade inflammatory processes promote the symptoms and progression of the disease. In this Review, the authors discuss the inflammatory pathophysiology in OA, including networks of inflammatory mediators in OA joints, transcriptional reprogramming of chondrocytes, and abnormal bioenergetics and proteostasis mechanisms, and consider the potential to target these processes for the treatment of OA. Chronic, low-grade inflammation in osteoarthritis (OA) contributes to symptoms and disease progression. Effective disease-modifying OA therapies are lacking, but better understanding inflammatory pathophysiology in OA could lead to transformative therapy. Networks of diverse innate inflammatory danger signals, including complement and alarmins, are activated in OA. Through inflammatory mediators, biomechanical injury and oxidative stress compromise the viability of chondrocytes, reprogramming them to hypertrophic differentiation and proinflammatory and pro-catabolic responses. Integral to this reprogramming are 'switching' pathways in transcriptional networks, other than the well-characterized effects of NFκB and mitogen-activated protein kinase signalling; HIF-2α transcriptional signalling and ZIP8-mediated Zn2+ uptake, with downstream MTF1 transcriptional signalling, have been implicated but further validation is required. Permissive factors, including impaired bioenergetics via altered mitochondrial function and decreased activity of bioenergy sensors, interact with molecular inflammatory responses and proteostasis mechanisms such as the unfolded protein response and autophagy. Bioenergy-sensing by AMPK and SIRT1 provides 'stop signals' for oxidative stress, inflammatory, and matrix catabolic processes in chondrocytes. The complexity of molecular inflammatory processes in OA and the involvement of multiple inflammatory mediators in tissue repair responses, raises daunting questions about how to therapeutically target inflammatory processes and macroscopic inflammation in OA. Bioenergy sensing might provide a pragmatic 'entry point'." @default.
• W2085294880 created "2016-06-24" @default.
• W2085294880 creator A5041517297 @default.
• W2085294880 creator A5079824415 @default.
• W2085294880 date "2014-09-30" @default.
• W2085294880 modified "2023-10-10" @default.
• W2085294880 title "Emerging regulators of the inflammatory process in osteoarthritis" @default.
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