PPAR- < em > γ < /em > Activation Alleviates Osteoarthritis through Both the Nrf2/NLRP3 and PGC-1 < em > α < /em > / < em > Δψ < /em > < sub > m < /sub > Pathways by Inhibiting Pyroptosis

In this study, we found that the level of NLRP3-mediated pyroptosis in severe lateral femoral condyle cartilage wear in the knee of an OA patient was significantly higher than that in the mild lateral femoral condyle cartilage wear areas. Moreover, in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced primary chondrocytes and knee OA rat models, we demonstrated that activation of PPAR-γ by pioglitazone (Piog) attenuated LPS/ATP-induced chondrocyte pyroptosis and arthritis. These effects were partially counteracted by either blocking the nuclear factor erythroid-2-related factor (Nrf2)/NLRP3 or PGC1-α/Δψ m signaling pathway. Simultaneous depression of these two signaling pathways can completely abrogate the protective effects of Piog on OA and chondrocytes. Taken together, Piog protects OA cartilage against pyroptosis-induced damage by simultaneously activating both the Nrf2/NLRP3 and PGC-1α/Δψ m pathways, which enhances antioxidative and anti-inflammatory responses as well as mitochondrial biogenesis. Therefore, Piog may be a promising agent for human OA cartilage damage in future clinical treatments.PMID:37020714 | PMC:PMC10070030 | DOI:10.1155/2023/2523536

Source: PPAR Research - April 6, 2023 Category: Genetics & Stem Cells Authors: Zhencheng Feng Qiuxiang Huang Xingliang Zhang Pengfei Xu Siming Li Dongli Ma Qingqi Meng Source Type: research