程韶, 杨骏杰, 王晶, 赵永见, 唐德志, 张岩, 赵东峰, 孙悦礼, 赵世天, 陶渝仁, 施杞, 舒冰, and 王拥军
Objective To investigate the effect and mechanism of local administration of oleanic acid on bone fracture healing in ovariectomized mice. Methods A total of 45 female C57BL/6 mice aged 3 months were randomly divided into sham group, model group and oleanic acid (OA) group, with 15 mice in each group. In the model group and OA group, osteoporosis model in mice was established by bilateral ovariectomy (OVX), while only parovarian adipose tissue was removed in the sham mice. Three months after OVX, a middle fracture model of the left tibia was established, and an implantable osmotic pump was implanted simultaneously during the operation, with local sustained-release of OA in OA group. At 14 and 28 days after the operation, the morphology of callus tissue, bone trabecular microstructure, pathological changes, and the expression levels of Notch signaling pathway target gene and osteogenic related genes were observed. Results The three-dimensional reconstruction of left tibia showed that the fracture lines of the sham group and OA group were fuzzy at 14 days after fracture, and a large number of callus were formed. The fracture line of model group was still clear. At 28 days after fracture, the callus of the sham group and OA group had almost finished remodeling, while there was still larger callus in the model group. The mRNA expression level of Notch signaling pathway target gene Hes1 and RUNt-related transcription factor 2 (Runx 2), osteocalcin (OCN) and alkaline phosphatase (ALP) in callus of the model group were increased by 14 days after fracture compared with those of sham operation group (P<0.05). Compared with the model group, the expression level of Hes1 mRNA in callus of the OA group was decreased (P<0.05), while the expression levels of Runx 2 and OCN mRNA were increased (P<0.05). At 28 days after fracture, there was no significant difference in the mRNA expression levels of Hes1 among different groups, and the mRNA expression levels of Runx2, ALP and OCN in the OA group and the model group were lower than those in the sham operation group (P<0.05), but there was no significant difference in the mRNA expression levels of Runx 2 and ALP between the OA group and the model group, while the mRNA expression level of OCN in the OA group was higher than that in the model group (P<0.05). At 14 days after fracture, gait analysis results showed that the average walking time of left posterior limb in OA group was less than that in model group (P<0.05). Conclusion Local sustained-release OA down-regulated the expression of the target gene of Notch signaling pathway, and up-regulate the expressions of osteogenic related genes, so as to promote the fracture healing of ovariectomized mice. [ABSTRACT FROM AUTHOR]