Autophagy and Angiogenesis in Oral and Maxillofacial Tissues: A Crucial Link to Periodontitis, OSF, and Wound Healing

Angiogenesis plays a critical role in maxillofacial regions and periodontal tissue reconstruction. However, dysregulation of angiogenesis in the oral cavity can lead to the development and progression of various pathologies, including oral submucous fibrosis (OSF) and maxillofacial cancer metastasis. Several studies have demonstrated the involvement of autophagy in angiogenesis in periodontitis, skin wound healing, oral mucosa, and oral cancer.

In chronic and aggressive forms of periodontitis, the expression of HIF-1α and VEGF increases significantly in gingival crevicular fluid and saliva. The microenvironment of periodontitis also leads to increased autophagy levels and angiogenin in PDLSCs. Autophagy enhancement increases the tube formation ability of PDLSCs, while autophagy blocking decreases angiogenesis in PDLSCs, potentially explaining the higher incidence of gingival bleeding in periodontitis patients.

In addition to periodontitis, autophagy is also involved in oral and maxillofacial skin and mucosal vascularization. One study demonstrated that autophagy promotes MSC-mediated vascularization by regulating VEGF secretion in cutaneous wound healing. Autophagy enhances the secretion of VEGF by MSCs through ERK phosphorylation, and the paracrine activity of VEGF in these MSCs is necessary for cutaneous wound healing. Another study found that arecoline, an endanger factor for OSF, induces over-activated autophagy in the oral cavity. High levels of autophagy reduce cell viability and inhibit angiogenesis in umbilical vein endothelial cells, potentially promoting OSF development in humans.