Role of hypoxia-induced collagen in chronic periodontal inflammation

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17065
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Osaka University
• Principal Investigator: Morimoto Chiaki 大阪大学, 歯学部附属病院, 医員 (70806801)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 低酸素 / 細胞外基質 / 歯周病

Outline of Final Research Achievements

In this study, we analyzed the effect of hypoxia-inducible factor (HIF), which has recently attracted attention as playing an important role in extracellular matrix production, on collagen synthesis and maturation in periodontal tissues. As a result, I revealed that activation of HIF-1 alpha resulted in increased expression of collagen prolyl 4-hydroxylase, alpha polypeptide I (P4HA1) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD2) in human gingival fibroblasts (HGF) and human periodontal ligament cells (HPDL). In HGF and HPDL cultured in hypoxic condition, increased expression of P4HA1, PLOD2 stimulated collagen production and cross-linking of collagen fiber, respectively.
There results suggested that when local oxygen concentration decreased in periodontal tissue, quantity and quality of collagen could be regulated by HIF.

Free Research Field

保存治療系歯学関連

Academic Significance and Societal Importance of the Research Achievements

歯周組織における低酸素下でのコラーゲン産生亢進の分子機序については、これまでに全く報告がなかった。そこで本研究では、HIFに着目し、HGF、HPDLを用いて低酸素下でのコラーゲン産生亢進の分子機序について解析を行った。本研究にて明らかとなったHIF-1alpha依存性P4HA1、PLOD2の産生亢進は、内因性の組織修復に重要な役割を担っていると考えられ、両分子の発現低下や機能不全が歯周病の重症化へ関与していると考えている。今後、両分子の歯周病病態形成過程における役割がin vivoにて明らかになれば、歯周組織における組織修復能を診査する新たな診断方法の確立につながるのではないかと考えている。