Triclosan alters antimicrobial and inflammatory responses of epithelial cells.

UNLABELLED: Periodontal diseases are a class of pathologies wherein oral microbes induce harmful immune responses in a susceptible host. Therefore, an agent that can both reduce microbial burden and lessen pathogenesis of localized inflammation would have beneficial effects in periodontal disease; 2,4,4-trichloro-2-hydroxydiphenyl-ether [triclosan] is currently used in oral care products owing to broad spectrum antimicrobial and anti-inflammatory properties. OBJECTIVE: To determine effects of triclosan on the response of oral epithelial cells to stimulation with the inflammatory microbial product lipopolysaccharide (LPS), a ligand for toll-like receptor 4 [TLR4]. MATERIALS/METHODS: Primary human oral epithelial cells were stimulated with LPS in the presence and/or absence of triclosan after which expression of pro-inflammatory cytokines, ß-defensins, micro-RNAs [miRNAs], or TLR-signaling pathway proteins were evaluated. RESULTS: Here, we demonstrate that triclosan is a potent inhibitor of oral epithelial cell LPS-induced pro-inflammatory responses by inducing miRNA regulation of the TLR-signaling pathway. Triclosan was not a pan-suppresser of oral epithelial cell responses as ß-defensin 2 [ßD2] and ßD3 were upregulated by triclosan following LPS-stimulation. CONCLUSIONS: These data demonstrate both a novel antimicrobial mechanism by which triclosan improves plaque control and an additional anti-inflammatory property, which could have beneficial effects in periodontal disease resolution.

Hyperglycemia induced and intrinsic alterations in type 2 diabetes-derived osteoclast function.

UNLABELLED: Periodontal disease-associated alveolar bone loss is a comorbidity of type-2-diabetes, where the roles of osteoclasts are poorly understood. OBJECTIVE: To evaluate osteoclast differentiation and function in the context of type-2-diabetes. MATERIALS AND METHODS: Bone marrow-derived osteoclasts from db/db mice, a model of type-2-diabetes, as well as human osteoclasts derived from peripheral blood of individuals with type-2-diabetes were evaluated for differentiation, resorption, and soluble mediator expression. RESULTS: While db/db mice were hyperglycemic at time of cell harvest, human participants were glycemically controlled. Although db/db cultures resulted in a higher number of larger osteoclasts, individual cell receptor activator of nuclear factor kappaB ligand (RANKL)-mediated bone resorption was similar to that observed in diabetes-free osteoclasts. Osteoclasts derived from individuals with type-2-diabetes differentiated similarly to controls with again no difference in bone resorbing capacity. Murine and human type-2-diabetes cultures both displayed inhibition of lipopolysaccharide (LPS)-induced deactivation and increased pro-osteoclastogenic mediator expression. CONCLUSIONS: Hyperglycemia plays a role in aberrant osteoclast differentiation leading to an increased capacity for bone resorption. Osteoclasts derived from murine models of and individuals with type-2-diabetes are unable to be inhibited by LPS, again leading to increased capacity for bone resorption. Here, environmental and intrinsic mechanisms associated with the increased alveolar bone loss observed in periodontal patients with type-2-diabetes are described.