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Hyperglycemia induced and intrinsic alterations in type 2 diabetes‐derived osteoclast function
Author(s) -
Catalfamo DL,
Britten TM,
Storch DI,
Calderon NL,
Sorenson HL,
Wallet SM
Publication year - 2013
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12002
Subject(s) - osteoclast , rankl , bone resorption , endocrinology , medicine , diabetes mellitus , resorption , type 2 diabetes , type 1 diabetes , dental alveolus , activator (genetics) , receptor , dentistry
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.