PSTPIP2 regulates synovial macrophages polarization and dynamics via ER[beta] in the joint microenvironment

Background 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 resistanc...

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Bibliographic Details
Published in:Arthritis research & therapy 2022-11, Vol.24 (1)
Main Authors: Yao, Yao, Cai, Xiaoyu, Zhang, Meng, Zhang, Xiao, Ren, Fujia, Zheng, Yan, Fei, Weidong, Zhao, Mengdan, Zheng, Caihong
Format: Article
Language:English
Subjects:
Analysis
Care and treatment
Cytoskeletal proteins
Development and progression
Health aspects
Macrophages
Physiological aspects
Rheumatoid arthritis
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Summary:Background 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. Methods In the current study, peripheral blood and surgically excised synovial tissue from RA patients, DBA/1 mice, Pstpip2.sup.CreR26-ZsGreen reporter mice, and Esr2.sup.fl/fl/Adgre-Cre tool mice were used for in vivo studies. Adeno-associated viral vector was used to overexpress PSPTIP2 protein in vivo. Results 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.sup.hi synovial macrophages form a tight immunological barrier in the lining layer. Notably, the ability of PSTPIP2 to regulate synovial macrophages polarization is dependent on ER[beta]. Additionally, PSTPIP2 regulates the dynamics of synovial macrophages via ER[beta]. Conclusions Together, this study reveals that PSTPIP2 regulates synovial macrophages polarization and dynamics via ER[beta] to form an immunological barrier (F4/80.sup.+PSTPIP2.sup.hi 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. Graphical PSTPIP2 regulates synovial macrophages polarization and dynamics via ER[beta] to form F4/80.sup.+PSTPIP2.sup.hi cellular barrier in joint microenvironment. Keywords: Synovial macrophages, PSTPIP2, Rheumatoid arthritis, Polarization, Dynamics, Estrogen receptor
ISSN:1478-6354
DOI:10.1186/s13075-022-02939-y