Exosomes mediate mitochondria dynamic and metabolic reprogramming for periodontal bone homeostasis

Abstract Background The crosstalk between periodontal ligament stem cells (PDLSCs) and macrophages plays an important role in periodontal bone homeostasis. Metabolic reprogramming is necessary for osteoclastic differentiation of macrophages. However, whether PDLSCs exert immunomodulatory function via modulating the metabolic reprogramming of macrophages is unknown. Methods PDLSCs from healthy individuals (H-PDLSCs) and patients with periodontitis (I-PDLSCs) were collected, then the exosomes were respectively isolated (H-Exo, I-Exo). The functions of H-Exo and I-Exo on the osteoclast function and periodontitis treatment were compared. The molecular mechanism of H-Exo on periodontitis was detected by microRNA sequence. And the metabolic reprogramming of macrophages was analyzed by seahorse test and 13C-glucose tracer. Results The results indicated that H-Exo inhibited osteoclastic differentiation and bone resorption in vitro and in vivo, while I-Exo has no obvious inhibitory effects. miRNA sequencing revealed that miR-92a-3p was a key molecule involved in the immunomodulatory effects of H-Exo. H-Exo modulates mitochondrial dynamics and cellular metabolism of macrophages via the miR-92a-3p/MFN1/PKM2 axis. Conclusions This study offers valuable insight into the crosstalk between PDLSCs and macrophages in periodontal bone homeostasis. In addition, this study also confirms that Exo from PDLSCs can modulate macrophage mitochondria dynamic and metabolism, which is a new way for PDLSCs to exert its immunoregulatory function.