Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways.

Although melatonin has a variety of biological actions such as antitumor, antiangiogenic, and antioxidant activities, the osteogenic mechanism of melatonin still remains unclear. Thus, in the present study, the molecular mechanism of melatonin was elucidated in the differentiation of mouse osteoblastic MC3T3-E1 cells. Melatonin enhanced osteoblastic differentiation and mineralization compared to untreated controls in preosteoblastic MC3T3-E1 cells. Also, melatonin increased wound healing and dose-dependently activated osteogenesis markers such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN), bone morphogenic protein (BMP)-2 and -4 in MC3T3-E1 cells. Of note, melatonin activated Wnt 5 α/ß, ß-catenin and the phosphorylation of c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a time-dependent manner while it attenuated phosphorylation of glycogen synthase kinase 3 beta (GSK-3ß) in MC3T3-E1 cells. Consistently, confocal microscope observation revealed that BMP inhibitor Noggin blocked melatonin-induced nuclear localization of ß-catenin. Furthermore, Western blotting showed that Noggin reversed activation of ß-catenin and Wnt5 α/ß and suppression of GSK-3ß induced by melatonin in MC3T3-E1 cells, which was similarly induced by ERK inhibitor PD98059. Overall, these findings demonstrate that melatonin promotes osteoblastic differentiation and mineralization in MC3T3-E1 cells via the BMP/ERK/Wnt pathways.

Evaluation of the effect of force direction on stationary anchorage success of mini-implant with a lever-arm-shaped upper structure.

OBJECTIVE: To compare the effect of clockwise and counterclockwise torque on the primary stability of a mini-implant with a lever-arm-shaped upper structure. MATERIALS AND METHODS: Twenty-four white rabbits were used for this study. Two screw-type mini-implants were placed in each tibia. In all, 96 screws were inserted. Two weeks later, a 2-N force was applied to the mini-implants without an upper structure in eight rabbits (control group). The mini-implants of the other 16 rabbits were loaded with an upper structure (experimental group). In the experimental group, the two left mini-implants were loaded in a clockwise direction (CW group) and the two right implants were loaded in a counterclockwise direction (CCW group). The rabbits were sacrificed at 1 week or 8 weeks after loading in both control and experimental groups. The removal torque value (RTV) was measured in 15 of 16 mini-implants in each group and the remaining implant was processed for histologic examination. RESULTS: At 1 week there were no significant differences in the mean RTV between the control, CW, and CCW groups. At 8 weeks, the RTV was higher in the control and experimental groups than in the respective 1-week groups. At 8 weeks, there were no significant differences in the RTV between the control and CW groups, but the CCW group showed a lower RTV. CONCLUSIONS: CCW torque can decrease the stability of a mini-implant, whereas a CW torque has no effect.