TY  - EJOU
AU  - Wang, Rihui 
AU  - Li, Wanlu 
AU  - Jiang, Canyang 
AU  - Huang, Jianping 
AU  - Zhou, Kangwei 
AU  - Jiang, Yan 
AU  - Zhang, Junyang 
AU  - Huang, Li 

TI  - CNPY2 Regulates Macrophage Polarization and Inflammatory Immune Responses via the TLR4/NF-κB Signaling Pathway to Alleviate Osteomyelitis of the Jaw
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - <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.
KW  - Canopy FGF signaling regulator 2 (CNPY2); osteomyelitis of the jaw (OMJ); toll-like receptor 4 (TLR4); nuclear factor-kappa B (NF-κB); <i>Staphylococcus aureus</i>; macrophage

DO  - 10.32604/biocell.2026.075875