Abstract
Osteomyelitis is a bone infection, most often caused by Staphylococcus aureus, in which neutrophils play a key role. Cathepsin G (CTSG) is a bactericidal serine protease stored in the neutrophil azurophilic granules. CTSG regulates inflammation, activating matrix metalloproteinases (MMPs), and coagulation. Lactoferrin (LF), a neutrophil glycoprotein, increases CTSG catalytic activity and induces inflammation. The aim of this study was to analyze a potential association between a CTSG gene polymorphism (Asn125Ser or N125S, rs45567233), that modifies CTSG activity, and could affect susceptibility to, or outcome of, bacterial osteomyelitis. CTSG N125S polymorphism was genotyped in 329 osteomyelitis patients and 415 controls), Blood coagulation parameters, serum CTSG activity, LF, MMP-1, MMP-13, and soluble receptor activator for nuclear factor κ B ligand (sRANKL) levels were assessed in carriers of the different CTSG genotypes. CTSG N125S (AG) genotype was significantly more frequent among osteomyelitis patients than controls (15.5% vs. 9.4%, p = 0.014). CTSG N125S variant G allele (AG +GG) was also more frequent among osteomyelitis patients (8.1% vs. 4.7%, p = 0.01). Serum CTSG activity and LF levels were significantly higher in osteomyelitis patients carrying the G allele compared to those with the AA genotype, (p<0.04). Serum MMP-1 was lower in the G allele carriers (p = 0.01). There was no association between these genotypes and clinical characteristics of osteomyelitis, or coagulation parameters, MMP-13, and sRANKL serum levels. Differences in the CTSG gene might enhance osteomyelitis susceptibility by increasing CTSG activity and LF levels.
Highlights
Cathepsin G (CTSG) is a 26-kDa serine protease stored in the azurophilic granules of the polymorphonuclear leukocytes
CTSG N125S polymorphism was genotyped in 329 osteomyelitis patients and 415 controls), Blood coagulation parameters, serum CTSG activity, LF, matrix metalloproteinases (MMPs)-1, MMP-13, and soluble receptor activator for nuclear factor κ B ligand levels were assessed in carriers of the different CTSG genotypes
CTSG N125S (AG) genotype was significantly more frequent among osteomyelitis patients than controls (15.5% vs. 9.4%, p = 0.014)
Summary
Cathepsin G (CTSG) is a 26-kDa serine protease stored in the azurophilic granules of the polymorphonuclear leukocytes It is released as a consequence of neutrophil stimulation by platelet-activating factor and different cytokines, and CTSG enhances platelet aggregation. CTSG has been reported to play an important role in a variety of inflammatory diseases including rheumatoid arthritis, coronary artery diseases, and ischemic reperfusion injury, and response to bone metastasis. It is implicated in several dental and respiratory infectious and inflammatory diseases, including periodontitis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and cystic fibrosis [1, 2]. The aim of this study was to analyze a potential association between a CTSG gene polymorphism (Asn125Ser or N125S, rs45567233), that modifies CTSG activity, and could affect susceptibility to, or outcome of, bacterial osteomyelitis
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