Simvastatin Maintains Osteoblastic Viability While Promoting Differentiation by Partially Regulating the Expressions of Estrogen Receptors α

Park, Jun‐Beom; Zhang, Huina; Lin, Chia Ying; Chung, Chong Pyoung; Byun, Youngro; Park, Yoon Shin; Yang, Victor C.

doi:10.1016/j.jss.2010.12.029

Cited by 39 publications

(42 citation statements)

References 18 publications

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“…34 There is strong evidence that statins increase the differentiation of osteoblasts and mineralization, resulting in osteogenesis. 35,36 In addition, statins increase osteogenesis indirectly by inhibiting inflammation which is responsible for an imbalance in the metabolism of bone. 37 Furthermore statins inhibit the activation of osteoclasts by inhibiting intracellular signaling pathways in osteoclasts 38 and have a role in maintaining the skeletal integrity.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold

Samiei¹,

Aghazadeh²,

Aminabadi³

et al. 2016

Adv Pharm Bull

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Section: Discussionmentioning

confidence: 99%

Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold

Samiei¹,

Aghazadeh²,

Aminabadi³

et al. 2016

Adv Pharm Bull

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“…So far, it has been reported that statin (lipophilic forms) upregulates ERa in osteoblasts, and captopril, an ACE inhibitor, downregulates the protein level of ER in ductual carcinoma cell lines. 59,60 Effects of these drugs on the cardiac ERs have not been investigated yet. However, this knowledge would be helpful to interpret the effects of E2 in atrial tissue.…”

Section: Study Limitationsmentioning

confidence: 99%

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men

Bukowska

Spiller²,

Wolke

et al. 2017

Exp Biol Med (Maywood)

175

183

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The present study demonstrates that estrogen affects the human atrial myocardium and mediates protective actions through estrogen receptors-(ER) dependent signaling. Estrogen substantially modulates the local RAS via downregulation of ACE and simultaneous upregulation of ACE2, AT2R and MAS expression levels. This is indicative of a shift of the classical RAS/ACE axis to the alternative, protective RAS/ACE2 axis. In support of this view, estrogen attenuated the expression of RAS-associated downstream effectors, LOX-1, and ICAM-1. A specific antagonist of ERa reversed the anti-inflammatory and anti-oxidative effects of estrogen in paced and nonpaced atrial tissue slices. In summary, our data demonstrate the existence of protective effects of estrogen in atrial tissue from elderly men which are at least in part, mediated by the regulation of local RAS homeostasis. AbstractData from animal experiments and clinical investigations suggest that components of the renin-angiotensin system are markedly affected by sex hormones. However, whether estrogen affects human atrial myocardium has not been investigated yet. In this study, we determined the effects of estrogen on key components of atrial renin-angiotensin system: angiotensin-converting enzyme, responsible for generation of angiotensin II and angiotensin-converting enzyme 2, counteracting majority of AngII effects, and different renin-angiotensin system receptors, AT1R, AT2R, and MAS. First, the expression levels of estrogen receptors mRNA were determined in right atrial appendages obtained from patients undergoing heart surgery. The amounts of estrogen receptor a and estrogen receptor b mRNA were similar between women (n ¼ 14) and men (n ¼ 10). Atrial tissue slices (350 mm) were prepared from male donors which were exposed to estrogen (1-100 nM; n ¼ 21) or stimulated at 4 Hz for 24 h in the presence or absence of 100 nM estrogen (n ¼ 16), respectively. The administration of estrogen did not change mRNA levels of estrogen receptors, but activated MAP kinases, Erk1/2. Furthermore, estrogen increased the amounts of angiotensin-converting enzyme 2-mRNA (1.89 AE 0.23; P < 0.05) but reduced that of angiotensin-converting enzyme-mRNA (0.78 AE 0.07, P < 0.05). In addition, the transcript levels of AT2R and MAS were upregulated by estrogen. Pacing of tissue slices significantly increased the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at both the mRNA and protein level. During pacing, administration of estrogen substantially lowered the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at the transcript (0.92 AE 0.21 vs. 2.12 AE 0.27 at 4 Hz) and protein level (0.94 AE 0.20 vs. 2.14 AE 0.3 at 4 Hz). Moreover, estrogen elicited anti-inflammatory and anti-oxidative effects on renin-angiotensin system-associated downstream effectors such as pro-oxidative LOX-1 and pro-inflammatory ICAM-1. An antagonist of estrogen receptor a reversed these anti-inflammatory and anti-oxidative effects of estrogen significantly. Overall, our results demo...

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“…Briefly, 20 μL of MTT solution (5 mg/mL) was added, followed by incubation for another 4 hours. After MTT-containing medium was removed and formazan was solubilized in 200 μL DMSO, The optical density values of solution were measured at a wavelength of 570 nm, and cell viability was calculated by the following equation: 23 Cell viability (%) OD570 (sample) OD570 control 100%.…”

Section: Cytotoxicity Of Plga Nps and Tc-plga Npsmentioning

confidence: 99%

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

Wang¹,

Liu²,

Tao³

et al. 2015

IJN

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Purpose Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis. Methods The molecular structures of TC–PLGA were validated by 1 H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method. The surface properties, cytotoxicity, cellular uptake, cell mineralization, bone targeting potential, and animal pharmacodynamics of the TC–PLGA NPs were evaluated and compared to those of PLGA NPs. Results It was confirmed that the average particle size of the NPs was approximately 220 nm. In phosphate-buffered saline (PBS, pH 7.4), the SIM-loaded NPs exhibited a cumulative release of up to 80% within 72 hours. An in vitro cell evaluation indicated that the NPs had an excellent cellular uptake capacity and showed great biocompatibility with MC3T3-E1 cells, thereby reducing the cytotoxic effects of SIM. The cell mineralization assay showed that the SIM-loaded NPs induced osteogenic differentiation and mineralized nodule formation in MC3T3-E1 cells, thereby achieving the same effect as SIM. Preliminary findings from in vitro and in vivo bone affinity assays indicated that the TC–PLGA NPs may display increased bone-targeting efficiency compared to PLGA NPs lacking a TC moiety. The use of SIM-loaded TC–PLGA NPs in treating osteoporosis was tested through animal pharmacodynamics analyses performed in ovariectomized rats, and the results suggested that the SIM-loaded TC–PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone. Conclusion Bone-targeting NPs, which were based on the conjugation of TC to PLGA copolymers, have the ability to target bone. These NPs may be developed as a delivery system for hydrophobic drugs, and they are expected to improve the curative effects of drugs, reduce the administered drug doses, and reduce side effects in other organs.

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Simvastatin Maintains Osteoblastic Viability While Promoting Differentiation by Partially Regulating the Expressions of Estrogen Receptors α

Cited by 39 publications

References 18 publications

Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold

Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

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