Targeting therapeutic agent against C3b/C4b, SB002, on the inflammation‐induced bone loss in experimental periodontitis

Abstract

Aims To use experimental periodontitis models in rats to investigate the correlation between local expression of the complement components C3b and C4b in periodontal tissues and disease severity, and to assess the therapeutic effects of targeting C3b/C4b on inflammatory bone loss. Materials and Methods The gingival expression of C3, C3b, and C4b in animal experimental periodontitis models were analysed immunohistochemically. The therapeutic effects of the C3b/C4b inhibitor (SB002) on ligation‐induced experimental periodontitis was examined using biochemical, histological, and immunohistochemical analyses. Results The gingival expression levels of C3, C3b, and C4b were positively correlated with the severity of periodontitis. Moreover, both single and multiple injections of the C3b/C4b inhibitor had preventive and therapeutic effects on alveolar bone loss in ligation‐induced experimental periodontitis with no associated adverse consequences. Conclusions The association between C3b/C4b and periodontitis may provide a basis for the development of novel therapeutic strategies for periodontitis and other inflammatory diseases.

Complement components C3b and C4b as potential reliable site‐specific diagnostic biomarkers for periodontitis

“…Improved understanding of the therapeutic effects of targeting the complement system, 17,22,28 consisting of C3b and C4b, on inflammatory bone loss in experimental periodontitis models may provide insight into the mechanism underlying the association of C3b/C4b with inflammatory bone loss. 17 To the best of our knowledge, this is the first study to confirm the correlation of the expression levels of C3b and C4b in human biosamples, GT (Figure 1) and GCF (Figure 3), with periodontitis severity and clinical periodontal parameters (e.g., PD and CAL) (Figures 2 and 4) and to recognize C3b and C4b as sitespecific diagnostic biomarkers for discrimination of diseased and non-diseased sites (Table 3). Our results indicated the novel diagnostic and therapeutic roles of C3b and C4b in periodontal disease, thereby paving the way for the screening, diagnosis, and management of periodontal disease in clinical perspectives and implications.…”

“…After washing, the sections were incubated with biotinylated anti-goat IgG, followed by incubation with labelled avidin, washed with PBS and visualized using 3,3′ diaminobenzidine (DAB) and hydrogen peroxide, counterstained with Harris' Hematoxylin for 15 s dehydrated, bleached in xylene and cover slipped. The immunohistochemical (IHC) score was determined as previously described, 17,36 which quantifying positive cells using the immunoreactive score (IRS) of by two independent pathologists using light microscope.…”

“…17 The findings indicated that complement components may be involved in the pathogenesis of periodontitis, and this association may provide a basis for the development of novel diagnostic and therapeutic strategies for periodontitis. 12,17,27,[29][30][31] However, studies on the expression levels of gingival C3b and C4b in disease progression and the correlation between the gingival C3b and C4b expression levels and clinical parameters in periodontitis are scarce.…”

“…Thus, they play a pivotal role in several infectious/inflammatory diseases, such as pathogenic Neisseria and Leptospira infections, macular degeneration, systemic lupus erythematosus, and periodontitis. 9,[14][15][16][17] Previous studies on the role of complement activation in periodontitis has focused on complement effector mechanisms that potentiate innate immunity against pathogens and the interaction between complement components and periodontal pathogens, such as P. gingivalis, Tannerella forsythia (T. forsythia), and Prevotella intermedia (P. intermedia). 9,[18][19][20][21][22] The progression of periodontal inflammation was associated with elevated C3 cleavage in gingival crevicular fluid (GCF), 23 whereas the increased complement activation (e.g., C3) in oral fluids was associated with the severity of periodontitis.…”

“…Cleavage products such as C3b and C4b opsonize the surface of recognized pathogenic substances and facilitate phagocytosis. Thus, they play a pivotal role in several infectious/inflammatory diseases, such as pathogenic Neisseria and Leptospira infections, macular degeneration, systemic lupus erythematosus, and periodontitis 9,14–17 …”