Plasmin Is Essential in Preventing Periodontitis in Mice

Abstract

Periodontitis involves bacterial infection, inflammation of the periodontium, degradation of gum tissue, and alveolar bone resorption, which eventually leads to loss of teeth. To study the role of the broad-spectrum protease plasmin in periodontitis, we examined the oral health of plasminogen (Plg)-deficient mice. In wild-type mice, the periodontium was unaffected at all time points studied; in Plg-deficient mice, periodontitis progressed rapidly, within 20 weeks. Morphological study results of Plg-deficient mice revealed detachment of gingival tissue, resorption of the cementum layer, formation of necrotic tissue, and severe alveolar bone degradation. IHC staining showed massive infiltration of neutrophils in the periodontal tissues. Interestingly, doubly deficient mice, lacking both tissue-and urokinase-type plasminogen activators, developed periodontal disease similar to that in Plg-deficient mice; however, mice lacking only tissueor urokinase-type plasminogen activator remained healthy. Supplementation by injection of Plg-deficient mice with human plasminogen for 10 days led to necrotic tissue absorption, inflammation subsidence, and full regeneration of gum tissues. Notably, there was also partial regrowth of degraded alveolar bone. Taken together, our results show that plasminogen is essential for the maintenance of a healthy periodontium and plays an important role in combating the spontaneous development of chronic periodontitis. Moreover, reversal to healthy status after supplementation of Plg-deficient mice with plasminogen suggests the possibility of using plasminogen for therapy of periodontal diseases.

Immunohistochemical analysis of the gingiva with periodontitis of type I plasminogen deficiency compared to gingiva with gingivitis and periodontitis and healthy gingiva

“…To date there have been many case reports reporting ligneous gingival lesions (El Darouti et al, 2009;Fine, Bauer, Al Mohaya, & Woo, 2009;Galeotti et al, 2014;Gokbuget et al, 1997;Gunhan et al, 1994Gunhan et al, , 1999Gunhan et al, 2012;Kurtulus et al, 2007;Scully et al, 2001;Silva, Bariani, Mendonca, & Batista, 2006;Suresh et al, 2003;Toker, Toker, Goze, Turgut, & Yilmaz, 2007), however, as far as we know, the possible role that plg may play in the maintenance of periodontal health has been first studied by Sulniute et al (2011) in mice. The authors were the first to show that the development of periodontitis in mice resembles that in humans and is characterized by the formation of necrotic tissue, the inflow of neutrophils, detachment of gingival tissue from the teeth, followed by severe alveolar bone resorption (Sulniute et al, 2011).…”

“…The authors were the first to show that the development of periodontitis in mice resembles that in humans and is characterized by the formation of necrotic tissue, the inflow of neutrophils, detachment of gingival tissue from the teeth, followed by severe alveolar bone resorption (Sulniute et al, 2011). In accordance with this result, in the present study, strong immunoreactivity of PMN elastase was detected in the high numbers of PMN leukocytes unequally distributed in the gingival tissue of gingival samples from patients with gingivitis, periodontitis and periodontitis with Plgdef (Fig.…”

“…Different types of bacteria are the initiators of the inflammatory process. Invading bacteria induce on one hand tissue damage by releasing lipopolysaccharides, effecting several cell types (fibroblasts, osteoblasts, osteoclasts) (Liu et al, 2009;Nair et al, 1996;Sulniute, Lindh, Wilczynska, Li, & Ny, 2011). On the other hand these lipopolysaccharides activate macrophages to release proinflammatory factors (Fujihara et al, 2003;Martinez, Sica, Mantovani, & Locati, 2008).…”

“…Neutrophils eliminate bacteria by phagocytosis and degranulation, however, some periodontopathogenic bacteria can evade the phagocytosis. This results in continuous accumulation of new neutrophils (Sulniute et al, 2011), which consist about 200 azurophilic, specific and secretory granules that contain a proteolytic enzyme (Herrmann, Gonzales, Boedeker, Vonholdt, & Meyle, 2001;Janoff, 1985). Neutrophil elastase (elastase 2) is the major proteolytic component of these cells (Herrmann et al, 2001).…”

Epithelial TRPV1 Signaling Accelerates Gingival Epithelial Cell Proliferation

“…Fixed mandibles were dissected, decalcified, embedded, and sectioned as previously described (Sulniute et al, 2011), with minor modifications. Paraffin sections were incubated with anti-TRPV1 antibody overnight.…”