Hypertension is a prevalent systemic disease in the elderly, who can suffer from several pathological skeletal conditions simultaneously, including osteoporosis. Benidipine (BD), which is widely used to treat hypertension, has been proved to have a beneficial effect on bone metabolism. In order to confirm the osteogenic effects of BD, we investigated its osteogenic function using mouse MC3T3-E1 preosteoblast cells in vitro. The proliferative ability of MC3T3-E1 cells was significantly associated with the concentration of BD, as measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell cycle assay. With BD treatment, the osteogenic differentiation and maturation of MC3T3-E1 cells were increased, as established by the alkaline phosphatase (ALP) activity test, matrix mineralized nodules formation, osteogenic genetic test, and protein expression analyses. Moreover, our data showed that the BMP2/Smad pathway could be the partial mechanism for the promotion of osteogenesis by BD, while BD might suppress the possible function of osteoclasts through the OPG/RANKL/RANK (receptor activator of nuclear factor- κB (NF-κB)) pathway. The hypothesis that BD bears a considerable potential in further research on its dual therapeutic effect on hypertensive patients with poor skeletal conditions was proved within the limitations of the present study.
高血压在老年人群中多发, 而不良骨质情况例如骨质疏松症也多见于老年患者。贝尼地平(Benidipine, BD)作为广泛使用的抗高血压药, 被发现具有一定的改善骨代谢的作用。为探究贝尼地平的促成骨作用, 本实验选用了小鼠MC3T3-E1前成骨细胞进行体外实验。MTT及细胞周期试验显示M3CT3-E1细胞增殖能力受BD影响显著提升且具有浓度依赖性。碱性磷酸酶活力试验、基质矿化试验、成骨相关基因和蛋白表达的测定发现, BD可促进MC3T3-E1细胞的成骨向分化和成熟。此外, 本项研究结果显示, BMP2/Smad通路在BD的促成骨效应中发挥作用, 而OPG/RANKL/RANK通路的改变提示BD可能通过抑制破骨细胞的活动间接改善骨代谢。综上, 在进一步研发治疗伴有不良骨质情况的高血压患者的双效药物方面, BD具有广阔的研究前景和应用潜力。
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This work was supported by the National Natural Science Foundation of China (Nos. 81600909 and 81800934) and the Zhejiang Provincial Medical Science and Technology Project of China (Nos. 2017RC009, 2018RC012, and 2021KY773).
Baixiang WANG, Jiakang YANG, and Yu WANG performed the experimental research and data analysis, wrote and edited the manuscript. Chenqiu ZHANG created the figures. Lijie FAN and Huiming WANG contributed to the study design, data analysis, and discussion. All authors have read and approved the final manuscript and, therefore, have full access to all data relevant to the study and take responsibility for the integrity and security of such data.
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Baixiang WANG, Jiakang YANG, Lijie FAN, Yu WANG, Chenqiu ZHANG, and Huming WANG declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Wang, B., Yang, J., Fan, L. et al. Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro. J. Zhejiang Univ. Sci. B 22, 410–420 (2021). https://doi.org/10.1631/jzus.B2000628