Xia Ya, Fan Danping, Li Xiaoya, Lu Xiangchen, Ye Qinbin, Xi Xiaoyu, Wang Qiong, Zhao Hongyan, Xiao Cheng
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Department of Emergency, China-Japan Friendship Hospital, Beijing, China.
Front Pharmacol. 2021 Dec 14;12:746786. doi: 10.3389/fphar.2021.746786. eCollection 2021.
Rheumatoid arthritis (RA) is characterized by an impaired articular bone immune microenvironment, which is associated with regulatory T cells (Tregs) hypofunction and osteoclasts (OCs) hyperfunction and leads to articular bone erosion and systemic bone loss. Studies have shown that Tregs slow bone loss in RA by regulating the bone resorption function of OCs and the JAK/STAT signaling pathway can regulate the immunosuppressive function of Tregs and reduce the bone erosion function of OCs. Yi Shen Juan Bi Pill (YSJB) is a classic Chinese herbal compound for the treatment of RA. However, whether YSJB regulates bone immune microenvironment homeostasis through JAK/STAT signaling pathway remains unclear. Based on OC single culture, Treg single culture and OC-Treg coculture systems, treatments were performed using drug-containing serum, AG490 and JAK2 siRNA to explore whether YSJB-containing serum regulates the homeostasis of the bone immune microenvironment through the JAK/STAT signaling pathway. , YSJB treatment decreased the number of TRAP cells and the areas of bone resorption and inhibited the expression of RANK, NFATc1, c-fos, JAK2, and STAT3 in both the OC single culture system and the OC-Treg coculture system. Tregs further reduced the number of TRAP cells and the areas of bone resorption in the coculture system. YSJB promoted the secretion of IL-10 while inhibiting the expression of JAK2 and STAT3 in Tregs. Moreover, inhibiting the expression of JAK2 with the JAK2 inhibitor AG490 and JAK2 siRNA improved the immunosuppressive functions of Treg, inhibited OC differentiation and bone resorption. Our study demonstrates that YSJB can regulate OC-mediated bone resorption and Treg-mediated bone immunity through the JAK2/STAT3 signaling pathway. This study provides a new strategy for regulating the bone immune microenvironment in RA with traditional Chinese medicine.
类风湿关节炎（RA）的特征是关节骨免疫微环境受损，这与调节性T细胞（Tregs）功能低下和破骨细胞（OCs）功能亢进相关，并导致关节骨侵蚀和全身性骨质流失。研究表明，Tregs通过调节OCs的骨吸收功能减缓RA中的骨质流失，且JAK/STAT信号通路可调节Tregs的免疫抑制功能并降低OCs的骨侵蚀功能。益肾蠲痹丸（YSJB）是治疗RA的经典中药复方。然而，YSJB是否通过JAK/STAT信号通路调节骨免疫微环境稳态仍不清楚。基于OC单培养、Treg单培养和OC-Treg共培养系统，使用含药血清、AG490和JAK2 siRNA进行处理，以探究含YSJB血清是否通过JAK/STAT信号通路调节骨免疫微环境的稳态。在OC单培养系统和OC-Treg共培养系统中，YSJB处理均减少了抗酒石酸酸性磷酸酶（TRAP）阳性细胞数量和骨吸收面积，并抑制了核因子κB受体活化因子（RANK）、活化T细胞核因子c1（NFATc1）、原癌基因c-fos、JAK2和信号转导子和转录激活子3（STAT3）的表达。Tregs进一步减少了共培养系统中TRAP阳性细胞数量和骨吸收面积。YSJB促进了白细胞介素10（IL-10）的分泌，同时抑制了Tregs中JAK2和STAT3的表达。此外，用JAK2抑制剂AG490和JAK2 siRNA抑制JAK2的表达改善了Treg的免疫抑制功能，抑制了OC分化和骨吸收。我们的研究表明，YSJB可通过JAK2/STAT3信号通路调节OC介导的骨吸收和Treg介导的骨免疫。本研究为用中药调节RA中的骨免疫微环境提供了一种新策略。
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