D L Catalfamo1, T M Britten, D L Storch, N L Calderon, H L Sorenson, S M Wallet. 1. Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.
Abstract
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.
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, humanparticipants 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 humantype-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.
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