Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and
its role in osteoclastogenesis
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.