Autophagy's Role in Oral Angiogenesis: Implications for Periodontitis, Wound Healing, and Oral Submucous Fibrosis

Maxillofacial alterations and periodontal tissue reconstruction are closely linked to angiogenesis, a crucial process in growth, tissue remodeling, and repair. However, dysregulation of angiogenesis in the oral cavity can lead to the development and progression of pathogenesis such as oral submucous fibrosis (OSF) and maxillofacial cancer metastasis [114]. Autophagy has been shown to play a role in angiogenesis in various oral tissues, including periodontitis, skin wound healing, oral mucosa, and cancer.

In a study of chronic and aggressive forms of periodontitis, HIF-1α and VEGF expression increased significantly in gingival crevicular fluid and saliva [115]. The autophagy level and angiogenin of PDLSCs were also increased in the periodontitis microenvironment [116]. Enhancement of autophagy increased the tube formation ability of PDLSCs, while blocking autophagy decreased angiogenesis in PDLSCs. This may explain why periodontitis patients are more susceptible to gingival bleeding.

Autophagy also plays a role in oral and maxillofacial skin and mucosal vascularization. A previous study found that autophagy promotes MSC-mediated vascularization by regulating VEGF secretion in cutaneous wound healing [117]. In skin endothelial cells, autophagy enhanced the secretion of VEGF by MSCs through ERK phosphorylation, and the paracrine activity of VEGF in these MSCs was necessary for cutaneous wound healing. Another study found that arecoline, an endanger factor for oral submucous fibrosis, induced over-activated autophagy in the oral cavity [118]. Further in vitro study showed that the high level of autophagy reduced cell viability and inhibited angiogenesis in umbilical vein endothelial cells, potentially promoting the development of oral submucous fibrosis in humans.