Effect of methoxy-polyethylene glycol-polylactic acid-bone protective protein nano micelle complex on osteoprotegerin and bone mineral density in osteoporotic rats

Abstract

This study assessed the effect of nanomicelle complex Methoxy-polyethylene glycol Polylactic acid bone protective protein on OPG and bone mineral density in osteoporotic rats. 35 rats were assigned into group A, B, C, D and E. Except for group A, Osteoarthritis (OA) rat models were established in all other groups. After modeling, group C, D and E were injected with PEG+OPG plasmid, PLL+OPG plasmid and PEG-PLL+ plasmid at 40 mg/kg dose of nanoparticles into mice via tail vein. The other groups were injected with an equal volume of NaCl solution to observe the bone density and OPG level. The bone trabeculae in the femoral tissues of group A were mostly plate-shaped and dense and uniform. Group B bones were sparse without new bone, while the trabecular bone in group C increased, the gap among trabecular bones decreased. The number of trabecular bones increased in group D, and new bone trabecula from group E increased, and arrangement was neat. Bone mineral density (BMD) and BMc levels in the femoral tissue from rats in group B decreased relative to group A (P <0.05), and the levels of BMD and BMc in the femoral tissue from rats in group C increased (P <0.05). BMD and BMc from mouse femur tissue were lower than group E (P <0.05). Moreover, Group B had a lower maximum load than group A (P <0.05) and group E was higher than group D (P <0.05). The femoral tissue structure of rats in group A was complete and bone matrix was arranged well without cavities. The number of bone cells in group B was reduced, while the bone matrix was disorderly distributed, and bones were fractured and more cavities were formed. Compared with group B, groups C, and D, and E had increased bone cells number and reduced bone matrix disorder improvement voids. Immunohistochemistry showed that, OPG increased in group B, and RANKL decreased (P <0.05), which was different from group A (P <0.05). OPG protein and mRNA from C, D and E groups decreased, and RANKL levels increased (P <0.05). PEG-PLL-OPG (PPO) significantly improved OP rat bone mineral density via regulation of BMD, BMc and biomechanical indicators, and the mechanism is related to increased OPG expression and reduced RANKL activity.