5-FU Weakens Defensive Functions of the Junctional Epithelium

Area of Science:

• Oral biology
• Periodontology
• Cancer therapy side effects

Background:

• Chemotherapy-induced oral mucositis and periodontitis are severe side effects of cancer treatment.
• The chemotherapeutic agent 5-Fluorouracil (5-FU) is known to cause systemic immune suppression.
• Additional factors contributing to these conditions beyond immune suppression require investigation.

Purpose of the Study:

• To investigate the role of junctional epithelium (JE) integrity and proliferation in chemotherapy-induced periodontitis.
• To determine the effects of topical versus systemic 5-Fluorouracil (5-FU) delivery on the JE and periodontium.

Main Methods:

• Topical and systemic administration of 5-Fluorouracil (5-FU) to the junctional epithelium (JE) in a preclinical model.
• Utilized EdU incorporation, quantitative immunohistochemistry (qIHC), histology, enzymatic assays, and micro-computed tomographic (μCT) imaging to assess JE structure and function.
• Compared 5-FU treated tissues with vehicle-treated controls.

Main Results:

• Systemic 5-FU inhibited JE cell proliferation, leading to atrophy and immune suppression.
• Topical 5-FU also inhibited JE cell proliferation, compromising barrier function and local immune response without systemic effects.
• Disruption of JE barrier function resulted in significant alveolar bone loss and increased bone porosity.

Conclusions:

• Reduced JE cell division directly compromises structural integrity and immune surveillance.
• This compromise contributes to the destruction of periodontal hard tissues, exacerbating periodontitis.
• JE proliferation is essential for maintaining periodontal homeostasis.