Hyperhomocysteinemia: Instigating the Mechanism of Periodontal Disease

Abstract

Periodontal disease is one of the most common conditions resulting from poor oral hygiene and is characterized by a destructive process in the periodontium which essentially include gingiva, alveolar mucosa, cementum, periodontal ligament, and the alveolar bone. Notably, the destructive event in the alveolar bone has been linked to homocysteine (Hcy) metabolism however; it has not yet been fully investigated. Therefore; the implication of Hcy towards initiation, progression, and maintenance of the periodontal disease remains incompletely understood. Our research has led to the discovery that hyperhomocysteinemia (HHcy) causes changes in the periodontal tissues as well as it leads to an increase in the angiogenesis‐related proteins, potentially indicating a faster onset of periodontal disease in the susceptible individuals. To study periodontal tissue status and angiogenesis‐related protein levels, we compared wild‐type C57BL/6J (WT) and CBS+/− (HHcy) mice strains. The distance between cementoenamel junction, and the alveolar bone crest (CEJ‐BC) were measured histomorphometrically using histological preparations (Hematoxylin and Eosin; H&E, and the Masson’s Trichrome staining). Serum angiogenesis‐related levels namely the angiogenin, angiopoietin‐1, endostatin/collagen XVIII, FGF acid, IGFBP‐1, IGFBP‐2, MMP‐9 (pro and active forms), PDGF‐AA, PDGF‐AB/PDGF‐BB, pentraxin‐3 were measured using the Proteome ProfilerTM Array Kit specific for the mouse. The data suggest an increase in the distance between cementoenamel junction, and the alveolar bone crest. Levels of the angiogenesis‐related proteins in CBS+/− mouse strain were also significantly increased in comparison to the WT control mice. Interestingly, some of these angiogenesis‐related proteins have been shown to be upregulated during the periodontal disease. Our findings thus underscore the importance of Hcy metabolism towards the loss of periodontal tissue homeostasis, and the causation of the periodontal disease indicating that regulating Hcy metabolism can help prevent periodontal tissue damage, and the periodontal disease in people who suffer from chronic metabolic disorders such as hyperhomocysteinemia.Support or Funding InformationFunding from the National Institutes of Health (NIH): HL139047, AR071789, HL74815, HL107640, HL139047, and DK116591.