Periodontal disease is a chronic inflammatory disorder characterized by progressive destruction of periodontal tissues, including alveolar bone resorption, primarily caused by dental biofilm accumulation. The progression of periodontal disease involves factors derived from periodontal pathogenic bacteria, coupled with environmental factors, such as smoking and stress. Additionally, host-dependent factors closely linked to the regulation of immune responses and inflammatory reactions play a critical role. Our research focused on elucidating the homeostatic mechanisms in periodontal tissues. We extensively studied the role of adenosine and the response of periodontal tissues to hypoxia. Through the activation of its receptors, adenosine modulates inflammatory reactions in the gingival fibroblasts and gingival epithelial cells. CD73, an enzyme responsible for extracellular production of adenosine, has been shown to play a role in promoting the differentiation of osteoblasts. Gingival epithelial cells cultured under hypoxic conditions showed suppressed IL-6 and IL-8 production induced by IL-1β in a hypoxia inducible factor-1α (HIF-1α) -dependent manner. We also found that in gingival fibroblasts and periodontal ligament cells, the production of extracellular matrices such as collagen and PLAP-1 was enhanced under hypoxia. The first half of this article provides an overview of our findings.
Although the progression of periodontal disease can be suppressed by mechanical removal of the dental biofilm, this alone cannot regenerate the lost periodontal tissue. Treatment involving guided tissue regeneration membranes or using enamel matrix proteins or fibroblast growth factor 2 can be effective for cases of mild-to-moderate periodontal tissue defects. However, there is no well-established regenerative therapy for severe periodontal tissue destruction. We have been working on the development of a therapy for severe periodontal disease involving autologous transplantation of adipose tissue-derived mesenchymal stem cells. In the second part of this article, we provide an overview of our research achievements, including the results from basic research and a clinical study, and introduce our current endeavors.
