Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, 310006, China.
Arthritis Res Ther. 2022 Nov 2;24(1):247. doi: 10.1186/s13075-022-02939-y.
The cytoskeletal protein, PSTPIP2, is associated with inflammation and is predominantly expressed in macrophages. Previous data have shown that PSTPIP2 inhibits articular bone damage in arthritic rats. The aim of this study is to explore the molecular mechanism of PSTPIP2's resistance to bone erosion.
In the current study, peripheral blood and surgically excised synovial tissue from RA patients, DBA/1 mice, Pstpip2R26-ZsGreen reporter mice, and Esr2/Adgre-Cre tool mice were used for in vivo studies. Adeno-associated viral vector was used to overexpress PSPTIP2 protein in vivo.
We found that The level of PSTPIP2 in synovial macrophages is negatively correlated with RA disease activity, which is mediated by synovial macrophages polarization. PSTPIP2 synovial macrophages form a tight immunological barrier in the lining layer. Notably, the ability of PSTPIP2 to regulate synovial macrophages polarization is dependent on ERβ. Additionally, PSTPIP2 regulates the dynamics of synovial macrophages via ERβ.
Together, this study reveals that PSTPIP2 regulates synovial macrophages polarization and dynamics via ERβ to form an immunological barrier (F4/80PSTPIP2 cell-enriched zone) for the joints. Thus, local modulation of PSTPIP2 expression in the joint microenvironment may be a potential strategy for controlling bone erosion in rheumatoid arthritis. PSTPIP2 regulates synovial macrophages polarization and dynamics via ERβ to form F4/80PSTPIP2 cellular barrier in joint microenvironment.
细胞骨架蛋白 PSTPIP2 与炎症有关，主要在巨噬细胞中表达。先前的数据表明，PSTPIP2 可抑制关节炎大鼠的关节骨损伤。本研究旨在探讨 PSTPIP2 抵抗骨侵蚀的分子机制。
本研究采用 RA 患者外周血和手术切除的滑膜组织、DBA/1 小鼠、Pstpip2R26-ZsGreen 报告小鼠和 Esr2/Adgre-Cre 工具小鼠进行体内研究。腺相关病毒载体用于体内过表达 PSTPIP2 蛋白。
我们发现滑膜巨噬细胞中 PSTPIP2 的水平与 RA 疾病活动呈负相关，这是由滑膜巨噬细胞极化介导的。PSTPIP2 滑膜巨噬细胞在衬里层形成紧密的免疫屏障。值得注意的是，PSTPIP2 调节滑膜巨噬细胞极化的能力依赖于 ERβ。此外，PSTPIP2 通过 ERβ调节滑膜巨噬细胞的动力学。
综上所述，本研究揭示了 PSTPIP2 通过 ERβ 调节滑膜巨噬细胞极化和动力学，在关节中形成免疫屏障（F4/80PSTPIP2 细胞丰富区）。因此，局部调节关节微环境中 PSTPIP2 的表达可能是控制类风湿关节炎骨侵蚀的一种潜在策略。PSTPIP2 通过 ERβ 调节滑膜巨噬细胞极化和动力学，在关节微环境中形成 F4/80PSTPIP2 细胞屏障。
