The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou 310006, China.
School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310006, China.
J Zhejiang Univ Sci B. 2021 May 15;22(5):410-420. doi: 10.1631/jzus.B2000628.
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.
高血压是老年人中常见的系统性疾病,他们可能同时患有几种病理骨骼疾病,包括骨质疏松症。贝尼地平(BD)广泛用于治疗高血压,已被证明对骨代谢有有益的影响。为了确认 BD 的成骨作用,我们在体外使用小鼠 MC3T3-E1 前成骨细胞研究了其成骨功能。噻唑蓝(MTT)测定和细胞周期测定表明,MC3T3-E1 细胞的增殖能力与 BD 的浓度显著相关。通过碱性磷酸酶(ALP)活性试验、基质矿化结节形成、成骨基因试验和蛋白表达分析,发现 BD 处理可增加 MC3T3-E1 细胞的成骨分化和成熟。此外,我们的数据表明,BMP2/Smad 通路可能是 BD 促进成骨作用的部分机制,而 BD 可能通过 OPG/RANKL/RANK(核因子-κB(NF-κB)受体激活剂)通路抑制破骨细胞的可能功能。在本研究的限制范围内,证明了 BD 在进一步研究其对骨骼状况不佳的高血压患者的双重治疗作用方面具有相当大的潜力。