@Article{biocell.2026.075875,
AUTHOR = {Rihui Wang, Wanlu Li, Canyang Jiang, Jianping Huang, Kangwei Zhou, Yan Jiang, Junyang Zhang, Li Huang},
TITLE = {CNPY2 Regulates Macrophage Polarization and Inflammatory Immune Responses via the TLR4/NF-κB Signaling Pathway to Alleviate Osteomyelitis of the Jaw},
JOURNAL = {BIOCELL},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/biocell/online/detail/26020},
ISSN = {1667-5746},
ABSTRACT = {<b>Background:</b> Osteomyelitis of the jaw (OMJ) is a severe infectious bone disease. While Canopy FGF signaling regulator 2 (CNPY2) is known to regulate inflammatory diseases, its role in OMJ remains unclear. The study aimed to investigate the role of CNPY2 in the mandibular joint and its molecular mechanisms. <b>Methods:</b> An <i>in vitro</i> OMJ model was generated by stimulating RAW264.7 macrophages with <i>S. aureus</i>. CNPY2 knockdown and overexpression models were established using siRNA and plasmids. Functional assays assessed cell proliferation, migration, and invasion. Macrophage polarization, cytokine secretion, and osteoclast differentiation were analyzed. The CNPY2-Toll-Like Receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) interaction was confirmed by Co-Immunoprecipitation (co-IP) and Western blot. <i>In vivo</i>, an OMJ mouse model was induced by <i>S. aureus</i> jaw injection and treated with si-CNPY2 lentivirus. Therapeutic effects were evaluated through histology and protein analysis. <b>Results:</b> <i>S. aureus</i> stimulation upregulated CNPY2 expression in RAW264.7 cells. Knockdown of CNPY2 inhibited <i>S. aureus</i>-induced cell proliferation, migration, and invasion, promoted macrophage polarization toward the M2 phenotype, suppressed M1 polarization, and reduced the release of pro-inflammatory cytokines. Additionally, CNPY2 knockdown inhibited <i>S. aureus</i>-induced osteoclast differentiation (decreased expression of markers such as Nuclear factor of activated T-cells cytoplasmic 1 [NFATc1] and Cathepsin K [CTSK]). Mechanistically, CNPY2 directly interacts with TLR4, and its knockdown suppresses activation of the TLR4/NF-κB axis. In the OMJ mouse model, CNPY2 knockdown significantly reduced inflammatory infiltration in the jaw, inhibited macrophage M1 polarization, and decreased osteoclastogenesis. <b>Conclusion:</b> CNPY2 exacerbates OMJ by enhancing macrophage M1 polarization, inflammation, and osteoclastogenesis via the TLR4/NF-κB axis. Targeting CNPY2 may offer a therapeutic strategy for <i>S. aureus</i>-induced OMJ.},
DOI = {10.32604/biocell.2026.075875}
}