Identification and characterization of novel salivary biomarkers for oral inflammatory disease

Abstract

Salivary biomarkers not only reflect the current status of periodontal diseases but may predict their progression and response to treatment. This study aimed to identify and characterize novel salivary biomarkers for periodontal diseases as a biomarker paradigm for an oral inflammatory disease. Proteome profiler arrays were used to study the protein profile of whole saliva from 12 patients with chronic periodontitis and 12 healthy subjects, and to identify novel salivary biomarkers for periodontal diseases. Results revealed that there were differences in the whole saliva protein profile between health and disease status. Salivary urokinase (uPA), urokinase receptor (uPAR), and vitamin D binding protein (VDBP) were among the highly expressed proteins in periodontitis. These proteins were identified as candidate salivary biomarkers for periodontal diseases. ELISA assays were used to quantify the candidate salivary biomarkers in 158 patients with periodontal diseases as compared to 103 healthy controls and were found to be significantly elevated in the patients (p<0.001). Salivary uPA levels but not uPAR and VDBP, were significantly downregulated following treatment of the patients (p<0.01). The uPA enzymatic activity was investigated in saliva of the patients and was found to be significantly elevated as compared to the controls (p<0.001). Salivary uPA, uPAR and VDBP levels and uPA activity were positively correlated with periodontal disease measures such as pocket depth. The in vitro stimulation of human gingival fibroblasts with P.gingivalis lipopolysaccharide induced the cells to produce higher levels of uPA and uPAR along with uPA activity as compared to unstimulated cells (p<0.01). In conclusion, salivary uPA, uPAR and VDBP in addition to uPA activity are suggested as biomarkers that may be useful in the diagnosis of periodontal diseases and can indicate their severity. Salivary uPA is a potential biomarker that can assess the response of periodontitis to treatment and may predict the disease progression.