Links Between Hypertension and Osteoporosis: Benidipine Ameliorates Osteoporosis in Ovariectomized Hypertensive Rats Through Promotion of Osteoblast Proliferation and Inhibition of Osteoclast Differentiation

Shimizu, Hideo; Nakagami, Hironori; Yasumasa, Natsuki; Mariana, Osako Kiyomy; Kyutoku, Mariko; Kuroda, Hiroshi; Nakagami, Futoshi; Shimamura, Munehisa; Rakugi, Hiromi; Morishita, Ryuichi

doi:10.1007/s12170-012-0248-y

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…In addition to the conventional antihypertensive function of BD, several studies have suggested that BD increases the ALP activity of osteoblastic cells and also stimulates mineral matrix deposition ( 19 , 20 ). In addition, BD has been shown to decrease receptor activator of nuclear factor κB ligand expression in human osteoblasts, indicating the suppression of osteoclast differentiation ( 21 ). The systematic experiments conducted in the present study also demonstrated that BD promoted the proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells at the cellular and molecular levels, when applied at concentrations of 1×10 −6 –1×10 −9 M. These findings indicate that BD may be a novel candidate for the combined treatment of osteoporosis and hypertension.…”

Section: Discussionmentioning

confidence: 99%

Effects of the antihypertensive drug benidipine on osteoblast function in vitro

Wang

Zhu³

et al. 2014

Experimental and Therapeutic Medicine

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The dihydropyridine-type calcium channel blocker, benidipine (BD) has been widely used in hypertension therapy. Previous studies have demonstrated that BD has a positive effect on bone metabolism. Inspired by this promoting phenomenon, the present study investigated the effects of BD on osteoblasts in vitro. Experiments were designed and performed, including an MTT assay, reverse transcription-polymerase chain reaction, western blot analysis, alkaline phosphatase activity measurements and alizarin red S staining. The results demonstrated that BD promoted osteoblast proliferation and osteogenic differentiation at concentrations from 1×10−6 to 1×10−9 M by upregulating Runx2, BMP2 and OCN gene expression levels. Overall, BD at appropriate concentrations has been demonstrated to have positive effects on osteoblast function in addition to its conventional clinical usage.

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Section: Discussionmentioning

confidence: 99%

Effects of the antihypertensive drug benidipine on osteoblast function in vitro

Wang

Zhu³

et al. 2014

Experimental and Therapeutic Medicine

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“…Several studies have proven that calcium channel blockers such as felodipine, cilnidipine, and benidipine can improve osteoporosis in ovariectomized mice by inhibiting osteoclasts [13][14][15]. A previous study by Takahashi et al [16] showed that Tet alleviated bone loss in sciaticneurectomized mice; however, this is a model of disused osteolysis.…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway

Liu

Guo

et al. 2020

Mediators of Inflammation

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Peri-implant osteolysis (PIO) and the subsequent aseptic loosening are the main reasons for artificial joint implant failure. Existing methods for treating aseptic loosening are far from satisfactory, necessitating advanced drug exploration. This study is aimed at investigating the effect and underlying mechanism of tetrandrine (Tet) on inflammatory osteolysis. We established a Ti particle-induced inflammatory osteolysis mouse model and administered Tet or an equal volume of phosphate-buffered saline (PBS). Two weeks later, specimens were collected. Histological staining showed that Tet administration inhibited Ti-stimulated osteolysis. Tartrate-resistant acid phosphate (TRAP) staining and transmission electron microscopy (TEM) demonstrated that osteoclast formation was remarkably inhibited in the groups treated with Tet in a dose-dependent manner. In addition, relevant inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) were also significantly reduced in the calvaria of the Tet-treated groups. Exposure of receptor activator for nuclear factor-κB ligand- (RANKL-) induced bone marrow-derived macrophages (BMMs) and RAW264.7 cells to Tet significantly reduced osteoclast formation, F-actin ring formation, bone resorption, and the expression of relevant genes (matrix metallopeptidase 9 (MMP-9), TRAP, and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1)) during osteoclastogenesis in vitro. Mechanistic studies using Western blotting demonstrated that Tet inhibited the nuclear factor (NF)-κB signaling pathway by decreasing the phosphorylation of inhibitor of NF-κB α (IκBα) and p65, which play important roles in osteoclast formation. Collectively, our data indicate that Tet suppressed Ti-induced inflammatory osteolysis and osteoclast formation in mice, suggesting that Tet has the potential to be developed to treat and prevent wear particle-induced inflammatory osteolysis.

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“…[4][5][6] In addition, BD has been reported to decrease RANKL (receptor activator of nuclear factor kappa-B ligand) expression in human osteoblasts, indicating the suppression of osteoclast differentiation. 7 Furthermore, BD promoted cell proliferation and osteogenic differentiation at concentrations from 1 • 10 -6 to 1 • 10 -9 M by upregulating gene expression levels of runt-related transcription factor-2 (RUNX2), bone morphogenetic protein (BMP)-2, and osteocalcin (OCN). 6 This increased the differentiation of bone marrow stromal cells (BMSCs) toward osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket

Imai

Ayukawa

Yasunami

et al. 2019

Advances in Wound Care

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Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BDloaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth.

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Links Between Hypertension and Osteoporosis: Benidipine Ameliorates Osteoporosis in Ovariectomized Hypertensive Rats Through Promotion of Osteoblast Proliferation and Inhibition of Osteoclast Differentiation

Cited by 5 publications

References 46 publications

Effects of the antihypertensive drug benidipine on osteoblast function in vitro

Effects of the antihypertensive drug benidipine on osteoblast function in vitro

Tetrandrine Inhibits Titanium Particle-Induced Inflammatory Osteolysis through the Nuclear Factor-κB Pathway

Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket

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