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2022, Vol. 26 ›› Issue (8): 1173-1179Effect of Zuogui Wan on bone morphogenetic protein 2 signaling pathway in ovariectomized osteoporosis miceLi Wei1, Zhu Hanmin2, Wang Xin1, Gao Xue1, Cui Jing1, Liu Yuxin1, Huang Shuming3
Abstract: BACKGROUND: Postmenopausal osteoporosis is a high-incidence disease in middle-aged and elderly women, which seriously affects the quality of life. It is very necessary to discover and develop an effective prevention and treatment method. Traditional Chinese medicine can treat postmenopausal osteoporosis with tonifying kidney medicines based on the theory of “kidney governs bone,” but the molecular mechanism is still unclear. OBJECTIVE: To observe the effect of Zuogui Wan on bone morphogenic protein 2 (BMP-2)/Runx-2/Osterix signaling pathway. METHODS: The postmenopausal osteoporosis model was established in mice by ovarian removal. Then the successfully modeled mice were divided into model group, sham operation group, estradiol group, high-, medium- and low-dose Zuogui Wan (0.936, 0.468, 0.234 g/L) groups, and blocker group, with 12 mice per group. In the high-, medium- and low-dose Zuogui Wan groups, the corresponding concentrations of Zuogui Wan decoction were given. Sham operation group and model group were given the equal volume of normal saline. Estradiol group was given estradiol aqueous solution. The blocker group was given ICI182780 plus high-dose Zuogui Wan decoction. Intervention in each group was given via gavage for 8 continuous weeks. Immunohistochemistry and western blot were used to detect the expression of key proteins BMP-2, Runx-2 and Osterix in the tibia and femur of ovariectomized osteoporosis mice after intervention by Zuogui Wan. Changes of protein expressions in the BMP pathway were detected after blocking estrogen receptor using ICI182780. RESULTS AND CONCLUSION: Immunohistochemical findings indicated that compared with the model group, the high and medium doses of Zuogui Wan could significantly increase the expression of BMP-2 in ovariectomized osteoporosis mice (P < 0.01, P < 0.05); the expression of Runx-2 in the medium- and low-dose Zuogui Wan groups was significantly different (P < 0.01). Western blot results showed that compared with the model group, the high and middle doses of Zuogui Wan significantly increased the expression of BMP-2 in ovariectomized osteoporosis mice (P < 0.05); the expression of Runx-2 was significantly higher in the high-, medium- and low-dose Zuogui Wan groups (P < 0.01, P < 0.05, P < 0.05); and the expression of Osterix was significantly higher in the high- and medium-dose Zuogui Wan groups (P < 0.01, P < 0.05). After ICI182780 intervention, compared with the high-dose group, the expression of BMP-2 and Runx-2 in the mouse tibia was significantly reduced in the blocker group (P < 0.05, P < 0.01) and the expression of BMP-2, Runx-2 and Osterix in the mouse femoral bones was significantly reduced in the blocker group (P < 0.01). To conclude, Zuogui Wan can participate in the regulation of bone metabolism by increasing the expression of important proteins in the BMP/Runx-2/Osterix signaling pathway in ovariectomized osteoporosis mice, thereby achieving the protection of bones. Key words:Zuogui Wan, osteoporosis, ovariectomy, bone morphogenic protein 2, Runx-2, Osterix |