Small Molecule Drugs and Autophagy: A New Frontier for Oral Tissue Regeneration

Various small molecule drugs have been utilized to alleviate survival stress in multiple oral tissue-related stem cells by activating autophagy. These drugs include synthetic protein/peptides and natural compounds derived from plants, which target different processes of autophagy to achieve balanced autophagy and ultimately enhance oral tissue regeneration.

Peptides and proteins such as IL-37, galectin-1, WP9QY peptide, and Copine-7 have been proven to enhance oral stem cell function by regulating autophagy. IL-37 promotes osteogenic and odontogenic differentiation of human DPSCs via autophagy, while Gal-1, a PPARbeta/delta agonist, acts as a RANKL and TNF-α antagonist to inhibit LPS-induced autophagy and apoptosis of human PDLSCs. WP9QY peptide inhibits osteoclastogenesis and osteoclast activity, and CPNE7 restores the physiological function of mature odontoblasts by inducing autophagy.

Moringin, an isothiocyanate extracted from Moringa oleifera seeds, has been found to regulate the function of oral tissue stem cells by manipulating autophagy pathways, such as PDLSCs and human gingival mesenchymal stem cells (hGMSCs). Studies have shown that moringin treatment down-regulates pro-apoptotic genes expression and up-regulates anti-apoptotic genes expression in human-PDLSCs by inducing mitophagy. Furthermore, moringin induces PDLSCs and hGMSCs towards neural progenitor differentiation, making it a potential therapeutic approach for neural injury. Next-Generation Sequencing (NGS) technology also revealed that moringin enhances the PI3K/AKT/mTOR signaling pathway, which is a vital signalling pathway for oral tissue regeneration.