Autophagy Regulation: Specific Treatments and Applications in Dentistry

In addition to the aforementioned methods, several specific treatments can regulate autophagy. Orthodontic tooth movement (OTM) is always accompanied by PDL and alveolar bone remodeling, and the compressive force occurring in OTM affects alveolar bone absorption and osteoclastogenesis. Chen et al. found that compressive force could induce autophagy activation in PDL tissues, which in turn enhanced bone density decrease and osteoclast activity via RANKL/OPG signaling pathway. Similarly, another study found that orthodontic loading activates autophagy in macrophages and osteoclasts through a force-dependent manner.

Extracellular matrix (ECM) is an important environmental cue for maintaining stem cells niche. Studies have revealed that ECM input, in conjunction with autophagic flux, is a key factor in optimizing MSC therapeutic approaches. The ECM contains collagen I, which downregulates autophagy, and ECM attachment loss could induce autophagy to protect against short-term anoikis. A review also pointed out that proteoglycans and other extracellular components can modulate autophagy activation under different cellular environments, regulating tumorigenesis and metastasis.

Other studies have demonstrated that hypoxia-induced autophagy is responsible for inflamed periapical lesion development and maintenance. LC3 was detected in human periapical lesions, and autophagy activates immune and inflammatory responses and protects cystic epithelial lining and capsule epithelial cells. Hypoxia-induced autophagy played a cytoprotective role and increased cell survival via the AMPK/mTOR pathway, allowing human DPSCs to resist nutrient depletion and hypoxia. Inhibition of autophagy abolished these protective roles.

Moreover, a previous study found that low-intensity pulsed ultrasound could decrease cartilage injury by upregulating autophagy biomarkers in rats with TMJ. Another study revealed that far-infrared exposure ameliorated burn wound healing by upregulating autophagy in differentiated THP-1 cells. Whether far-infrared can be used for skin and oral mucosa regeneration by activating autophagy requires further investigation.