Betulinic Acid Attenuates Osteoarthritis via Limiting NLRP3 Inflammasome Activation to Decrease Interleukin-1β Maturation and Secretion

作者：Bo Liu, Yanglin Wu, Ting Liang, Yunlong Zhou, Guangdong Chen, Jiaheng He, Chenchen Ji, Peixin Liu, Chenhui Zhang, Jun Lin, Kece Shi, Zong‐Ping Luo, Naicheng Liu, Xinlin Su · 发表于：Mediators of Inflammation · 年份：2023 · DOI：10.1155/2023/3706421 · 被引用次数：15 · 研究领域：Inflammasome and immune disorders、Autoimmune and Inflammatory Disorders Research、Natural product bioactivities and synthesis

Introduction. Osteoarthritis (OA) is the most common degenerative joint disorder. Prior studies revealed that activation of NLRP3 inflammasome could promote the activation and secretion of interleukin-1β (IL-1β), which has an adverse effect on the progression of OA. Betulinic acid (BA) is a compound extract of birch, whether it can protect against OA and the mechanisms involved are still unknown. Materials and Methods. In vivo experiments, using gait analysis, ELISA, micro-CT, and scanning electron microscopy (SEM), histological staining, immunohistological (IHC) and immunofluorescence (IF) staining, and atomic force microscopy (AFM) to assess OA progression after intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. In vitro experiments, caspase-1, IL-1β, and the N-terminal fragment of gasdermin D (GSDMD-NT) were measured in bone marrow-derived macrophages (BMDMs) by using ELISA, western blot, and immunofluorescence staining. Results. We demonstrated that OA progression can be postponed with intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. Specifically, BA postponed DMM-induced cartilage deterioration, alleviated subchondral bone sclerosis, and relieved synovial inflammation. In vitro studies, the activated NLRP3 inflammasome produces mature IL-1β by facilitating the cleavage of pro-IL-1β, and BA could inhibit the activation of NLRP3 inflammasome in BMDMs. Conclusions. Taken together, our analyses revealed that BA attenuates OA via limiting...