Background
Autophagy has recently emerged as a protective mechanism in response to compressive force and an important process in maintenance of bone homeostasis. It appears to be involved in the degradation of osteoclasts, osteoblasts, and osteocytes. The aim of this study was to investigate the role of compressive forceâinduced autophagy in periodontal ligament (PDL) cells in regulating osteoclastogenesis of orthodontic tooth movement (OTM).
Methods
An OTM model and compressive force on PDL cells were employed to investigate the expression of autophagy markers in vivo and in vitro, respectively. Autophagosomes and autolysosomes were observed in PDL cells by transmission electron microscope (TEM) and autophagy LC3 double labelling. 3âMethyladenine (3âMA) and rapamycin were respectively used to inhibit and promote autophagy, and the effect of autophagy on osteoclastogenesis was explored via microcomputed tomography, hematoxylin and eosin (H&E) staining, histochemistry of titrateâresistant acid phosphatase, and realâtime polymerase chain reaction (RTâPCR) in vivo. Receptor activator of nuclear factorâkappa B ligand/osteoprotegerin (RANKL/OPG) was investigated by RTâPCR and ELISA in vitro.
Results
Orthodontic forceâinduced autophagy was prominent on the pressured side of PDL tissues. Administration of 3âMA downregulated bone density and upregulated osteoclasts, while rapamycin had reverse results in OTM. The autophagy activity increased initially then decreased in PDL cells during compressive force application and responded to light force. In PDL cells, administration of 3âMA upregulated while rapamycin downregulated the RANKL/OPG ratio.
Conclusion
Autophagy is activated by compressive force in PDL cells. Besides, it could modulate OTM by negatively regulating osteoclastogenesis and keep bone homeostasis via RANKL/OPG signaling.