Oral Tissue Regeneration: Small-Molecule Drugs and Autophagy Activation

Multiple small-molecule drugs have been utilized to alleviate survival stress by activating autophagy in various oral tissue-related stem cells. These drugs include synthetic protein/peptides and natural compounds derived from plants. By targeting different processes of autophagy, these small-molecule drugs aim to achieve a balanced autophagy, ultimately enhancing oral tissue regeneration.

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

Moringin, an isothiocyanate extracted from Moringa oleifera seeds, has also been found to regulate the function of oral tissue stem cells by manipulating autophagy pathways. Studies have shown that moringin can induce mitophagy in human PDLSCs, down-regulating pro-apoptotic genes expression and up-regulating anti-apoptotic genes expression. Moreover, moringin has been found to induce both PDLSCs and hGMSCs towards neural progenitor differentiation, making it a promising therapeutic approach for neural injury. Next-Generation Sequencing (NGS) technology has revealed that moringin enhances the PI3K/AKT/mTOR signaling pathway, crucial for oral tissue regeneration.