Effects of the 1, 4-dihydropyridine L-type calcium channel blocker benidipine on bone marrow stromal cells
Effects of the 1, 4-dihydropyridine L-type calcium channel blocker benidipine on bone marrow stromal cells
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DOI：
10.1007/s00441-015-2115-x
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发表时间：
2015-08-01
影响因子：
3.6
通讯作者：
Cai, Dao-zhang
中科院分区：
文献类型：
--
作者：
Ma, Zhong-ping;Liao, Jia-cheng;Cai, Dao-zhang
骨质疏松症 (OP) 通常会增加骨折和其他并发症的风险，是一个主要的临床问题。先前的研究发现，高血压与骨形成异常有关，导致钙流失增加。我们研究了抗高血压药物贝尼地平在骨质疏松条件下对骨髓基质细胞（BMSC）分化为成骨细胞和骨形成的影响。我们采用体外和体内相结合的方法来检验贝尼地平促进小鼠 BMSC 分化为成骨细胞的假设。在成骨条件下培养 2 周的 C57/BL6 小鼠原代股骨 BMSC 中评估碱性磷酸酶 (ALP)、骨钙素 (OCN)、runt 相关转录因子 2 (RUNX2)、β-连环蛋白和低密度脂蛋白受体相关蛋白 5 (LRP5) 蛋白表达，以检查贝尼地平的作用。使用卵巢切除（OVX）小鼠模型来研究贝尼地平治疗3个月的体内效果。我们发现体外和体内 ALP、OCN 和 RUNX2 表达上调，WNT/β-连环蛋白信号传导增强。与对照组 OVX 小鼠相比，灌胃给予贝尼地平的 OVX 小鼠，股骨远端干骺端的骨参数（小梁厚度、骨矿物质密度和小梁数量）显着增加。一致地，贝尼地平促进 BMSC 分化为成骨细胞，并防止 OVX 小鼠骨质流失。因此，贝尼地平可能是治疗绝经后骨质疏松症和高血压患者的合适候选药物。
Osteoporosis (OP) often increases the risk of bone fracture and other complications and is a major clinical problem. Previous studies have found that high blood pressure is associated with bone formation abnormalities, resulting in increased calcium loss. We have investigated the effect of the antihypertensive drug benidipine on bone marrow stromal cell (BMSC) differentiation into osteoblasts and bone formation under osteoporotic conditions. We used a combination of in vitro and in vivo approaches to test the hypothesis that benidipine promotes murine BMSC differentiation into osteoblasts. Alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), beta-catenin, and low-density lipoprotein receptor-related protein 5 (LRP5) protein expression was evaluated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of benidipine. An ovariectomized (OVX) mouse model was used to investigate the effect of benidipine treatment for 3 months in vivo. We found that ALP, OCN, and RUNX2 expression was up-regulated and WNT/beta-catenin signaling was enhanced in vitro and in vivo. In OVX mice that were intragastrically administered benidipine, bone parameters (trabecular thickness, bone mineral density, and trabecular number) in the distal femoral metaphysis were significantly increased compared with control OVX mice. Consistently, benidipine promoted BMSC differentiation into osteoblasts and protected against bone loss in OVX mice. Therefore, benidipine might be a suitable candidate for the treatment of patients with postmenopausal osteoporosis and hypertension.