Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging
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ORIGINAL ARTICLE
Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging Juliet Akkaoui & Chiaki Yamada & Carolina Duarte & Anny Ho & Saynur Vardar-Sengul & Toshihisa Kawai & Alexandru Movila Received: 31 March 2020 / Accepted: 20 August 2020 # American Aging Association 2020
Abstract Aging is associated with increased prevalence and severity of pathogenic outcomes of periodontal disease, including soft tissue degeneration and bone loss around the teeth. Although lipopolysaccharide (LPS) derived from the key periodontal pathogen Porphyromonas gingivalis (Pg) plays an important role in the promotion of inflammation and osteoclastogenesis via toll-like receptor (TLR)4 signaling, its pathophysiological role in age-associated periodontitis remains unclear. This study investigated the possible effects of Pg-LPS on RANKL-primed osteoclastogenesis and ligature-induced periodontitis in relation to aging using young (2 months old) and aged (24 months old) mice. To the best of our knowledge, our results indicated that expression of TLR4 was significantly diminished on the surface of osteoclast precursors isolated from aged mice compared with that of young mice. Furthermore, our data demonstrated that the TLR4 antagonist (TAK242) dramatically decreased the numbers of tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts differentiated from RANKL-primed young J. Akkaoui : C. Yamada : C. Duarte : A. Ho : S. Vardar-Sengul : T. Kawai : A. Movila (*) College of Dental Medicine, Nova Southeastern University, 3200 S University Dr.,, Ft. Lauderdale, FL 33324, USA e-mail: [email protected] A. Movila Institute for Neuro-Immune Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA A. Movila The Forsyth Institute, Cambridge, MA, USA
osteoclast precursors (OCPs) compared with those isolated from aged mice in response to Pg-LPS. In addition, using a ligature-induced periodontitis mouse model, we demonstrated that Pg-LPS elevated (1) secretion of senescence-associated secretory phenotype (SASP) markers, including the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, as well as osteoclastogenic RANKL, and (2) the number of OCPs and TRAP+ osteoclasts in the periodontal lesion induced in young mice. In contrast, Pg-LPS had little, or no, effect on the promotion of periodontitis inflammation induced in aged mice. Altogether, these results indicated that periodontal disease in older mice occurs in a manner independent of canonical signaling elicited by the Pg-LPS/ TLR4 axis. Keywords Aging . Porphyromonas gingivalis lipopolysaccharide . Periodontitis . Osteoclastogenesis . Bone loss
Introduction Periodontal disease is one of the most prevalent chronic age-associated infectious diseases affecting humans. Pathologic manifestations are characterized by soft tissue degeneration and alveolar bone loss around the teeth in association with oral microbial dysbiosis [11]. Alarming epidemiological data indicates that around 70% of senior patients at age over 65 years old suffe
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