2022, Vol. 26 ›› Issue (32): 5173-5178

Bone metabolism in a rat model of diabetes mellitus intervened by Xianling Gubao Capsules

Jiao Yinghua1, Bao Kairan2, Song Jieqiong2, Xing Lei1, Cui Lihua2, Gao Jingyuan1, Qi Ning1, Liu Xiangyu1   

Abstract: BACKGROUND: Xianling Gubao Capsules (a commonly used Chinese medicine in orthopedic surgery) can improve bone metabolism and prevent osteoporosis; however, whether it has a preventive effect or a possible mechanism on osteoporosis complicated by diabetes has been rarely reported.
OBJECTIVE: To investigate the effects of Xianling Gubao Capsules on bone metabolism and related osteogenic marker factors Wnt3a, β-catenin and bone morphogenetic protein-2 in rats with diabetes mellitus complicated by osteoporosis and to explore their mechanisms of action.
METHODS: Thirty-six male healthy 8-week-old Sprague-Dawley rats were treated with streptozotocin at a dose of 60 mg/kg to establish a diabetes mellitus model and were then randomly divided into model group, Xianling Gubao Capsule group and alendronate group, with 12 rats in each group. Another 12 normal rats were used as the normal group. Rats in the Xianling Gubao Capsule group and alendronate group were given Xianling Gubao Capsule and alendronate sodium suspension by gavage for 12 weeks, respectively. Rats in the normal and model groups were gavaged with the same amount of double-distilled water for 12 weeks. Blood glucose level of model rats was measured once a week during the administration period to ensure the accuracy of the experiment. Femur, tibia and systemic bone mineral density in each group were measured by dual energy X-ray absorptiometry. Hematoxylin-eosin staining was used to observe the morphological changes of the right femur in each group. Immunohistochemistry and RT-PCR were applied to detect the expression of osteogenic marker factors Wnt3a, β-catenin, and bone morphogenetic protein-2 at protein and mRNA levels.  
RESULTS AND CONCLUSION: Compared with the model group, the femur, tibia and systemic bone mineral density values of rats increased significantly in the Xianling Gubao Capsule group (P < 0.05). The mRNA and protein expressions of Wnt3a, β-catenin, and bone morphogenetic protein-2 in bone tissues decreased significantly in the model group (P < 0.05). While compared with the model group, the mRNA and protein expressions of Wnt3a, β-catenin, and bone morphogenetic protein-2 were significantly increased in the Xianling Gubao Capsule group (P < 0.05). In addition, there was no significant difference in the expressions of above-mentioned indicators between the Xianling Gubao Capsule group and alendronate group. These findings confirmed that Xianling Gubao Capsules exert a protective effect on bone metabolism in diabetic rats by the Wnt /β-catenin signaling pathway.
Key words: diabetes, osteoporosis, Wnt/β-catenin, signaling pathway, Xianling Gubao Capsules, rat