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Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis
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  • Lin Sun,
  • Xinyu Wang,
  • Ning He,
  • Zhuo An,
  • Ruohan Yu,
  • Changhong Li,
  • Yanming Li,
  • Yongjun Li,
  • Xiangyuan Liu,
  • dong Fang,
  • Jinxia Zhao
Lin Sun
Peking University Third Hospital
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Xinyu Wang
Peking University Third Hospital
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Ning He
Beijing Institute of Genomics Chinese Academy of Sciences
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Zhuo An
Peking University Third Hospital
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Ruohan Yu
Peking University Third Hospital
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Changhong Li
Peking University Third Hospital
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Yanming Li
Beijing Institute of Genomics Chinese Academy of Sciences
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Yongjun Li
Beijing Institute of Genomics Chinese Academy of Sciences
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Xiangyuan Liu
Peking University Third Hospital
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dong Fang
Beijing Institute of Genomics Chinese Academy of Sciences
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Jinxia Zhao
Peking University Third Hospital
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Abstract

Background. Anti-citrullinated protein/peptide antibodies (ACPA) play important roles in the pathogenesis of rheumatoid arthritis (RA). ACPA-positive (ACPA+) and ACPA-negative (ACPA-) RA were suggested to be different disease subsets with distinct differences in genetic variation and clinical outcomes. The aims of the present study were to compare gene expression profiles in ACPA+ and ACPA- RA and identify novel candidate gene signatures that might serve as therapeutic targets. Methods. Comprehensive transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from ACPA+ and ACPA- RA patients, and healthy controls was performed via RNA sequencing. A validation cohort was used to further investigate differentially expressed genes via PCR and ELISA. Spearman’s correlation test was used to evaluate the correlation of differentially expressed genes and the clinical and laboratory data of the patients. The role of differentially expressed genes in osteoclastogenesis was further investigated. Results. Expression of C-X-C motif chemokine ligand 2 (CXCL2) was significantly increased in ACPA+ RA than in ACPA- RA, which was validated in PBMCs and serum. CXCL2 promoted the migration of CD14+ monocytes and increased osteoclastogenesis in RA patients. RAW264.7 macrophages were used to investigate specific mechanisms, and the results suggested that CXCL2 stimulated osteoclastogenesis via ERK MAPK and NFκB pathways. Conclusion. CXCL2 was highly expressed in ACPA+ RA than in ACPA- RA. CXCL2 promoted osteoclastogenesis and was related to bone erosion in RA, which suggest that the blockade of CXCL2 might be a novel strategy for the treatment of RA.

Peer review status:ACCEPTED

22 Apr 2020Submitted to Clinical & Experimental Immunology
22 Apr 2020Submission Checks Completed
22 Apr 2020Assigned to Editor
27 Apr 2020Reviewer(s) Assigned
26 May 2020Review(s) Completed, Editorial Evaluation Pending
26 May 2020Editorial Decision: Revise Major
23 Aug 20201st Revision Received
01 Sep 2020Reviewer(s) Assigned
13 Sep 2020Review(s) Completed, Editorial Evaluation Pending
13 Sep 2020Editorial Decision: Accept