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On-line Access: 2021-05-07

Received: 2020-10-10

Revision Accepted: 2021-01-08

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Huiming WANG

https://orcid.org/0000-0002-1131-7455

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.5 P.410-420

http://doi.org/10.1631/jzus.B2000628


Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro


Author(s):  Baixiang WANG, Jiakang YANG, Lijie FAN, Yu WANG, Chenqiu ZHANG, Huiming WANG

Affiliation(s):  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; more

Corresponding email(s):   whmwhm@zju.edu.cn

Key Words:  Benidipine, Osteoblast, Osteogenesis, MC3T3-E1


Baixiang WANG, Jiakang YANG, Lijie FAN, Yu WANG, Chenqiu ZHANG, Huiming WANG. Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro[J]. Journal of Zhejiang University Science B, 2021, 22(5): 410-420.

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author="Baixiang WANG, Jiakang YANG, Lijie FAN, Yu WANG, Chenqiu ZHANG, Huiming WANG",
journal="Journal of Zhejiang University Science B",
volume="22",
number="5",
pages="410-420",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000628"
}

%0 Journal Article
%T Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro
%A Baixiang WANG
%A Jiakang YANG
%A Lijie FAN
%A Yu WANG
%A Chenqiu ZHANG
%A Huiming WANG
%J Journal of Zhejiang University SCIENCE B
%V 22
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%P 410-420
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000628

TY - JOUR
T1 - Osteogenic effects of antihypertensive drug benidipine on mouse MC3T3-E1 cells in vitro
A1 - Baixiang WANG
A1 - Jiakang YANG
A1 - Lijie FAN
A1 - Yu WANG
A1 - Chenqiu ZHANG
A1 - Huiming WANG
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 5
SP - 410
EP - 420
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000628


Abstract: 
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.

降压药贝尼地平在体外对小鼠MC3T3-E1细胞促成骨作用的初步研究

概要: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。

关键词:贝尼地平;成骨细胞;骨质疏松症;M3CT3-E1

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AfzalF, PratapJ, ItoK, et al., 2005. Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription. J Cell Physiol, 204(1):63-72.

[2]BoyleWJ, SimonetWS, LaceyDL, 2003. Osteoclast differentiation and activation. Nature, 423(6937):337-342.

[3]CaoX, ChenD, 2005. The BMP signaling and in vivo bone formation. Gene, 357(1):1-8.

[4]ChenMM, ZhangYH, DuYP, et al., 2019. Epidemiological and clinical study of hip fracture in hospitalized elderly patients in Shanghai, China. Arch Osteoporos, 14:37.

[5]ChenP, LiZZ, HuYH, 2016. Prevalence of osteoporosis in China: a meta-analysis and systematic review. BMC Public Health, 16:1039.

[6]ChenX, WangZQ, DuanN, et al., 2018. Osteoblast‒osteoclast interactions. Connect Tissue Res, 59(2):99-107.

[7]CuiZY, MengXY, FengH, et al., 2019. Estimation and projection about the standardized prevalence of osteoporosis in mainland China. Arch Osteoporos, 15:2.

[8]DucyP, StarbuckM, PriemelM, et al., 1999. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev, 13(8):1025-1036.

[9]GaoSW, LiuF, 2019. Novel insights into cell cycle regulation of cell fate determination. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(6):467-475.

[10]GhoshM, MajumdarSR, 2014. Antihypertensive medications, bone mineral density, and fractures: a review of old cardiac drugs that provides new insights into osteoporosis. Endocrine, 46(3):397-405.

[11]HiguchiA, LingQD, HsuST, et al., 2012. Biomimetic cell culture proteins as extracellular matrices for stem cell differentiation. Chem Rev, 112(8):4507-4540.

[12]HuangZN, RenPG, MaT, et al., 2010. Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability. Cytokine, 51(3):305-310.

[13]IlićK, ObradovićN, Vujasinović-StuparN, 2013. The relationship among hypertension, antihypertensive medications, and osteoporosis: a narrative review. Calcif Tissue Int, 92(3):217-227.

[14]InayoshiA, SugimotoY, FunahashiJ, et al., 2011. Mechanism underlying the block of human Cav3.2 T-type Ca2+ channels by benidipine, a dihydropyridine Ca2+ channel blocker. Life Sci, 88(19-20):898-907.

[15]KosakaH, HirayamaK, YodaN, et al., 2010. The L-, N-, and T-type triple calcium channel blocker benidipine acts as an antagonist of mineralocorticoid receptor, a member of nuclear receptor family. Eur J Pharmacol, 635(1-3):49-55.

[16]LarijaniB, BekheirniaMR, SoltaniA, et al., 2004. Bone mineral density is related to blood pressure in men. Am J Hum Biol, 16(2):168-171.

[17]LeeKS, HongSH, BaeSC, 2002. Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-β and bone morphogenetic protein. Oncogene, 21(47):7156-7163.

[18]LimLS, FinkHA, BlackwellT, et al., 2009. Loop diuretic use and rates of hip bone loss and risk of falls and fractures in older women. J Am Geriatr Soc, 57(5):855-862.

[19]LiuL, WangD, QinY, et al., 2019. Astragalin promotes osteoblastic differentiation in MC3T3-E1 cells and bone formation in vivo. Front Endocrinol, 10:228.

[20]LynnH, KwokT, WongSYS, et al., 2006. Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone, 38(4):584-588.

[21]MaJ, WangZ, ZhaoJQ, et al., 2018. Resveratrol attenuates lipopolysaccharides (LPS)‍-induced inhibition of osteoblast differentiation in MC3T3-E1 cells. Med Sci Monit, 24:2045-2052.

[22]MaJY, YouD, LiWY, et al., 2019. Bone morphogenetic proteins and inner ear development. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(2):131-145.

[23]MaZP, LiaoJC, ZhaoC, et al., 2015. Effects of the 1,4-dihydropyridine L-type calcium channel blocker benidipine on bone marrow stromal cells. Cell Tissue Res, 361(2):467-476.

[24]MetzJA, MorrisCD, RobertsLA, et al., 1999. Blood pressure and calcium intake are related to bone density in adult males. Br J Nutr, 81(5):383-388.

[25]MundyGR, ChenD, ZhaoM, et al., 2001. Growth regulatory factors and bone. Rev Endocr Metab Disord, 2(1):105-115.

[26]NeveA, CorradoA, CantatoreFP, 2013. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol, 228(6):1149-1153.

[27]NishiyaY, SugimotoS, 2001. Effects of various antihypertensive drugs on the function of osteoblast. Biol Pharm Bull, 24(6):628-633.

[28]NishiyaY, KosakaN, UchiiM, et al., 2002. A potent 1,4-dihydropyridine L-type calcium channel blocker, benidipine, promotes osteoblast differentiation. Calcif Tissue Int, 70(1):30-39.

[29]NoëlD, GazitD, BouquetC, et al., 2004. Short-term BMP-2 expression is sufficient for in vivo osteochondral differentiation of mesenchymal stem cells. Stem Cells, 22(1):74-85.

[30]ShimizuH, NakagamiH, YasumasaN, et al., 2012. Links between hypertension and osteoporosis: benidipine ameliorates osteoporosis in ovariectomized hypertensive rats through promotion of osteoblast proliferation and inhibition of osteoclast differentiation. Curr Cardiovasc Risk Rep, 6(4):274-280.

[31]SimsNA, GooiJH, 2008. Bone remodeling: multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol, 19(5):444-451.

[32]SudoH, KodamaHA, AmagaiY, et al., 1983. In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol, 96(1):191-198.

[33]SuzukiH, YokoyamaK, AkimotoY, et al., 2007. Clinical efficacy of benidipine for vasospastic angina pectoris. Arzneimittelforschung, 57(1):20-25.

[34]TetiA, 2011. Bone development: overview of bone cells and signaling. Curr Osteoporos Rep, 9(4):264-273.

[35]WangBX, BiM, ZhuZ, et al., 2014. Effects of the antihypertensive drug benidipine on osteoblast function in vitro. Exp Ther Med, 7(3):649-653.

[36]WangZW, ChenZ, ZhangLF, et al., 2018. Status of hypertension in China: results from the China hypertension survey, 2012‒2015. Circulation, 137(22):2344-2356.

[37]WuMR, ChenGQ, LiYP, 2016. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res, 4:16009.

[38]XueC, ZhouCC, YangB, et al., 2017. Comparison of efficacy and safety between benidipine and hydrochlorothiazide in fosinopril-treated hypertensive patients with chronic kidney disease: protocol for a randomised controlled trial. BMJ Open, 7(2):e013672.

[39]YangSM, NguyenND, EismanJA, et al., 2012. Association between beta-blockers and fracture risk: a Bayesian meta-analysis. Bone, 51(5):969-974.

[40]YaoK, NagashimaK, MikiH, 2006. Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci, 100(4):243-261.

[41]YuD, WangJ, QianKJ, et al., 2020. Effects of nanofibers on mesenchymal stem cells: environmental factors affecting cell adhesion and osteogenic differentiation and their mechanisms. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(11):871-884.

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