[PROMOTION EFFECT OF FTY-720P ON TREATMENT OF BONE DEFECT WITH ALLOGRAFT BONE BY SUPPRESSING OSTEOCLAST FORMATION AND...

To explore whether FTY-720P could enhance the effect of allograft bone for bone defect repair by suppressing osteoclast formation and function.

Animal experiment: Forty-eight New Zealand white rabbits were selected to establish the tibia defect model (1.5 cm in length) and were divided into 4 groups (n = 12). Defect was not repaired in group A, defect was repaired with allograft bone in group B, with autogenous fibula in group C, and with allograft bone and FTY-720P in group D. Lane-Sandhu scoring system and bone density examination were used to evaluate the effect at 2, 4, 8, and 12 weeks after operation. Cell experiment: Bone marrow-derived mononuclear phagocytes (BMMs) were harvested from 1-month-old Sprague Dawley rats and induced into osteoclasts with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κ B ligand (RANKL), then were identified with tartrate-resistant acid phosphatas (TRAP). According to different concentrations of FTY-720P before induction, experiment was divided into 0, 500, 600, 700, 800, 900, 1,000, and 1,500 ng/mL groups. The effect of FTY-720P was studied by counting the number of osteoclasts and the number of bone resorption lacunae made by osteoclasts.

Animal experiment: Lane-Sandhu score showed no significant difference between groups at 2 weeks after operation (P > 0.05), but the score was significantly better in groups C and D than groups A and B, and in group B than group A (P < 0.05). The bone density of group C was significantly greater than that of groups A, B, and D at 2 weeks after operation (P < 0.05), but no significant difference was found among groups A, B, and D (P > 0.05); the bone density of groups B, C, and D was significantly greater than that of group A at 4, 8, and 12 weeks (P < 0.05), but no significant difference was shown among groups B, C, and D (P > 0.05). Cell experiment: BMMs could be induced into osteoclasts by the addition of M-CSF and RANKL, which could be proved by counting the number of the nuclear and TRAP staining. The osteoclasts were significantly more in 0, 500, 600, 700, 800, 900 ng/mL groups than 1 000 and 1 500 ng/mL groups (P < 0.05), in 0, 500, 600, and 700 ng/mL groups than 800 and 900 ng/mL groups (P < 0.05), in 0, 500, 600 ng/mL groups than 700 ng/mL group (P < 0.05); and there was no significant difference between the other groups (P > 0.05). The number of bone resorption lacunae in 0, 500, 600, and 700 ng/mL groups was significantly higher than that in 800, 900, 1,000, and 1,500 ng/mL groups (P < 0.05), and it was significantly higher in 0, 500 and 600 ng/mL groups than 700 ng/mL group (P < 0.05), but difference was not significant between the other groups (P > 0.05).

FTY-720P combined with allograft bone for bone defect repair can have the same effect to autogenous bone by means of inhibiting osteoclast formation and function, which reduces bone loss.