ResearchIn-Press Preview Open Access | 10.1172/jci.insight.181940
1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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1Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, United States of America
2Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, Indianapolis, United States of America
3Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, United States of America
4Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, United States of America
5Department of Otolaryngology-Head & Neck Surgery, Indiana University, Indianapolis, United States of America
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Published July 18, 2024 - More info
Type 2 diabetes (T2D) is on the rise worldwide and is associated with various complications of the oral cavity. Using an adult-onset diabetes preclinical model, we demonstrated profound periodontal alterations in T2D mice, including inflamed gingiva, disintegrated periodontal ligaments (PDL), marked alveolar bone loss, and unbalanced bone remodeling due to decreased formation and increased resorption. Notably, we observed elevated levels of the Wnt signaling inhibitor sclerostin in the alveolar bone of T2D mice. Motivated by these findings, we investigated whether a sclerostin-neutralizing antibody (Scl-Ab) could rescue the compromised periodontium in T2D mice. Administering Scl-Ab subcutaneously once a week for four weeks, starting four weeks after T2D induction, led to substantial increases in bone mass. This effect was attributed to the inhibition of osteoclasts and promotion of osteoblasts in both control and T2D mice, effectively reversing the bone loss caused by T2D. Furthermore, Scl-Ab stimulated PDL cell proliferation, partially restored the PDL fibers, and mitigated inflammation in the periodontium. Our study thus established a T2D-induced periodontitis mouse model characterized by inflammation and tissue degeneration. Scl-Ab emerged as a promising intervention to counteract the detrimental effects of T2D on the periodontium, exhibiting limited side effects on other craniofacial hard tissues.