Ophiopogonin D improves osteointegration of titanium alloy implants under diabetic conditions by inhibition of ROS overproduction via Wnt/ß-catenin signaling pathway.

A high failure rate of titanium implants in diabetic patients has been indicated in clinical evidences. Excessive oxidative stress at the bone-implant interface plays an important role in the impaired osteointegration under diabetic conditions. While the underlying mechanisms remain unknown and the targeted treatments are urgently needed. Ophiopogonin D (OP-D), isolated from Chinese herbal Radix Ophiopogon japonicus, is generally reported to be a potent antioxidant agent. In the present study, we hypothesized that OP-D exerted promotive effects on osteointegration against oxidative stress, and investigated the underlying mechanisms associated with alteration of Wnt/ß-catenin signaling pathway. Rabbit osteoblasts incubated on titanium alloy implant were co-cultured with normal serum (NS), diabetic serum (DS), DS + OP-D, DS + NAC (a potent ROS inhibitor) and DS + OP-D + Dkk1 (a Wnt inhibitor) for examinations of osteoblast behaviors. For in vivo study, titanium alloy implants were implanted into the femoral condyle defects on diabetic rabbits. Results demonstrated that diabetes-induced oxidative stress resulted in osteoblast dysfunctions and apoptotic injury at the bone-implant interface, concomitant with the inactivation of Wnt/ß-catenin signaling. Importantly, OP-D administration attenuated oxidative stress, directly reactivating Wnt/ß-catenin signaling. Osteoblast dysfunctions were thus reversed as evidenced by improved osteoblast adhesion, proliferation and differentiation, and ameliorated apoptotic injury, exerting similar effects to NAC treatment. In addition, the positive effects afforded by OP-D were confirmed by improved osteointegration and oetogenesis within the titanium alloy implants in vivo by Micro-CT and histological analyses. Furthermore, the pro-osteogenic effects of OP-D were almost completely abolished by the Wnt inhibitor Dkk1. These results demonstrated, for the first time, OP-D administration alleviated the damaged osteointegration of titanium alloy implants under diabetic conditions by means of inhibiting oxidative stress via a Wnt/ß-catenin-dependent mechanism. The OP-D administration would become a reliable treatment strategy for implant failure therapy in diabetics due to the optimal anti-oxidative and pro-osteogenic properties.

Influence of the shape of the micro-finite element model on the mechanical properties calculated from micro-finite element analysis.

Assessing the biomechanical properties of trabecular bone is of major biological and clinical significance for the research of bone diseases, fractures and their treatments. Micro-finite element (µFE) models are becoming increasingly popular for investigating the biomechanical properties of trabecular bone. The shapes of µFE models typically include cube and cylinder. Whether there are differences between cubic and cylindrical µFE models has not yet been studied. In the present study, cubic and cylindrical µFE models of human vertebral trabecular bone were constructed. A 1% strain was prescribed to the model along the superior-inferior direction. E values were calculated from these models, and paired t-tests were performed to determine whether these were any differences between E values obtained from cubic and cylindrical models. The results demonstrated that there were no statistically significant differences in the E values between cubic and cylindrical models, and there were no significant differences in Von Mises stress distributions between the two models. These findings indicated that, to construct µFE models of vertebral trabecular bone, cubic or cylindrical models were both feasible. Choosing between the cubic or cylindrical µFE model is dependent upon the specific study design.