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 NLRP3 inflammasome activation to decrease the IL-1β maturation and secretion.

中文翻译：

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桦木酸通过限制 NLRP3 炎性体激活以减少 IL-1β 成熟和分泌来减轻骨关节炎

介绍。骨关节炎（OA）是最常见的退行性关节疾病。此前的研究表明，NLRP3炎症小体的激活可以促进白细胞介素1β（IL-1β ）的激活和分泌，从而对OA的进展产生不利影响。桦木酸（BA）是桦木的复合提取物，其是否具有预防骨关节炎的作用及其机制尚不清楚。材料和方法。体内实验，使用步态分析、ELISA、显微 CT 和扫描电子显微镜 (SEM)、组织学染色、免疫组织学 (IHC) 和免疫荧光 (IF) 染色以及原子力显微镜 (AFM) 评估腹腔注射后 OA 进展在 OA 小鼠模型中，BA 浓度为 5 和 15 mg/kg。体外实验中，使用 ELISA、蛋白质印迹和免疫荧光染色测量骨髓源性巨噬细胞 (BMDM) 中的 caspase-1、IL-1 β 和 Gasdermin D N 末端片段 (GSDMD-NT) 。结果。我们证明，在 OA 小鼠模型中腹腔注射 5 和 15 mg/kg BA 可以推迟 OA 进展。具体来说，BA 延缓了 DMM 引起的软骨退化，减轻了软骨下骨硬化，并缓解了滑膜炎症。体外研究发现，激活的NLRP3炎症小体通过促进pro-IL-1β的裂解产生成熟的IL- 1β，并且BA可以抑制BMDMs中NLRP3炎症小体的激活。结论。综上所述，我们的分析表明，BA 通过限制 NLRP3 炎性体激活来减少 IL-1 β 的成熟和分泌，从而减轻 OA。