Influence of parstatin on experimental periodontal disease and repair in rats.

BACKGROUND: Parstatin is a 41-amino acid peptide, formed by proteolytic cleavage on activation of the protease activated receptor-1, with antiangiogenic properties. The purpose of this study is to evaluate the influence of synthetic parstatin on experimental periodontal disease and repair in rats. METHODS: Ligature-induced periodontitis was established in rats and the influence of parstatin administration was assessed after 8 and 15 days for periodontal disease and 24 hours and 8 days after repair after ligature removal. RESULTS: Parstatin administration significantly inhibited gingival myeloperoxidase activity, interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 levels and led to suppression of macrophages and collagen degradation. At periodontal tissues under repair, parstatin increased the gingival levels of endostatin and decreased vascular endothelial growth factor expression and blood vessel number but did not influence histologic healing. In addition, the tomographic linear bone loss was significantly reduced at 15 days of periodontitis when the rats were treated with parstatin compared to their respective phosphate-buffered saline-treated controls. CONCLUSIONS: Parstatin suppresses the periodontal tissue breakdown followed by experimental periodontitis in rats and did not impair periodontal tissue repair, despite its antiangiogenic effect. Parstatin may represent a novel approach to modulate host response in chronic periodontal disease.

Expression of protease activated receptor-1 in chronic periodontitis.

BACKGROUND: Protease activated receptor-1 (PAR1) activation by thrombin may play a role in repair and homeostasis of periodontal tissues. The main objective of this study is to investigate PAR1 expression in patients with periodontitis, before and after non-surgical periodontal treatment, and to associate its expression with the presence of inflammatory biomarkers and PAR2 expression. METHODS: Gingival crevicular fluid (GCF) samples and clinical parameters, including probing depth, clinical attachment level, bleeding on probing, and gingival and plaque indices, were collected from periodontally healthy individuals and patients with moderate chronic periodontitis (CP) before and 6 weeks after periodontal non-surgical treatment. PAR1 and PAR2 messenger RNA (mRNA) at the GCF were evaluated by quantitative polymerase chain reaction (qPCR). Flow cytometry analysis identified the GCF PAR1-expressing cells. GCF inflammatory biomarkers were also determined. RESULTS: Clinical parameters were significantly improved after therapy (P <0.01). The qPCR analysis showed that, before therapy, PAR1 mRNA levels in CP were similar to controls. Periodontal treatment led to increased PAR1 expression in CP (P <0.05). PAR1 expression was inversely correlated to PAR2 expression and with interleukins 6 and 8, tumor necrosis factor-α, interferon-γ, and matrix metalloproteinase-2 levels. CONCLUSIONS: Periodontal treatment results in PAR1 overexpression in the GCF, and PAR1 expression is associated with decreased expression of inflammatory biomarkers and inversely correlated to PAR2 expression in the GCF. Therefore, the data suggest the importance of PAR1 mediating the known anabolic actions of thrombin in the periodontium.