Bone marrow stromal cells from low-turnover osteoporotic mouse model are less sensitive to the osteogenic effects of fluvastatin.
Bone marrow stromal cells from low-turnover osteoporotic mouse model are less sensitive to the osteogenic effects of fluvastatin.
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DOI：
10.1371/journal.pone.0202857
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Yajima Y
中科院分区：
文献类型：
--
作者：
Oda Y;Sasaki H;Miura T;Takanashi T;Furuya Y;Yoshinari M;Yajima Y
本研究旨在观察氟伐他汀对加速衰老小鼠模型SAMP 6和正常加速衰老小鼠模型SAMR 1骨髓基质细胞（BMSCs）向成骨细胞分化的影响。SAMP菌株自发地从AKR/J背景中产生，与对照SAMR菌株相比，显示出缩短的寿命和一系列加速老化的迹象。还评估了氟伐他汀的剂量效应。在有/无氟伐他汀（0 μM、0.1 μM、0.5 μM和1.0 μM）的情况下培养BMSC。进行基于WST-1的比色法以评价细胞增殖。为了评估细胞分化，通过定量逆转录聚合酶链反应（qRT-PCR）测定bmp 2和runx 2的基因表达水平，并使用酶联免疫吸附试验（BMP 2）和免疫荧光染色（BMP 2和Runx 2）测定蛋白质表达水平。碱性磷酸酶（ALP）活性测定和组织化学检测，用碱性磷酸酶组织化学检测检测的BMP特异性拮抗剂noggin的作用。为了评估成熟成骨标志物，通过qRT-PCR测定bglap 2的基因表达水平，并通过茜素红染色测定矿化。RhoA活性也通过Western印迹法检测。在SAMP 6中，氟伐他汀显著增加BMP 2、Runx 2和Bglap 2的mRNA和蛋白表达，并且BMP 2的作用增加ALP活性。RhoA活性也被氟伐他汀抑制。足以增加BMP 2和Runx 2表达和ALP活性的氟伐他汀浓度在SAMP 6中为0.5 μM，在SAMR 1中为0.1 μM。结论：氟伐他汀通过RhoA-BMP 2途径促进BMSC向成骨细胞分化。SAMP 6的BMSCs对氟伐他汀的成骨作用不如SAMR 1敏感。
This study aimed to investigate the effects of fluvastatin on the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts in senescence-accelerated mouse prone 6 (SAMP6) compared with that in the normal senescence-accelerated-resistant mouse (SAMR1) model. SAMP strains arose spontaneously from the AKR/J background and display shortened life span and an array of signs of accelerated aging, compared with control SAMR strains. The dose effects of fluvastatin were also evaluated. BMSCs were cultured with/without fluvastatin (0 μM, 0.1 μM, 0.5 μM, and 1.0 μM). WST-1-based colorimetry was performed to evaluate cell proliferation. To evaluate cell differentiation, gene expression levels of bmp2 and runx2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and protein expression levels were determined using enzyme-linked immunosorbent assay (BMP2) and immunofluorescence staining (BMP2 and Runx2). Alkaline phosphatase (ALP) activity assay and histochemical detection were determined; the effect of noggin, a BMP-specific antagonist, was examined using ALP histochemical detection. To assess for mature osteogenic marker, gene expression levels of bglap2 were determined by qRT-PCR and mineralization was determined by alizarin red staining. RhoA activity was also examined by Western blotting. In SAMP6, BMP2, Runx2 and Bglap2 mRNA and protein expressions were significantly increased by fluvastatin, and ALP activity was increased by BMP2 action. RhoA activity was also inhibited by fluvastatin. The concentration of fluvastatin sufficient to increase BMP2 and Runx2 expression and ALP activity was 0.5 μM in SAMP6 and 0.1 μM in SAMR1. In conclusion, the present study revealed that fluvastatin promoted BMSC differentiation into osteoblasts by RhoA-BMP2 pathway in SAMP6. BMSCs of SAMP6 are less sensitive to the osteogenic effects of fluvastatin than SAMR1.
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影响因子：
3.3
作者：
Kasai, S;Shimizu, M;Hosokawa, M
通讯作者：
Hosokawa, M
影响因子：
5.3
作者：
Kupcsik L;Meurya T;Flury M;Stoddart M;Alini M
通讯作者：
Alini M
DOI：
10.1006/bbrc.2001.5597
发表时间：
2001-09-21
影响因子：
3.1
作者：
Ohnaka, K;Shimoda, S;Takayanagi, R
通讯作者：
Takayanagi, R
影响因子：
56.9
作者：
Mundy, G;Garrett, R;Gutierrez, G
通讯作者：
Gutierrez, G
影响因子：
4.8
作者：
Ghosh-Choudhury, Nandini;Mandal, Chandi Charan;Choudhury, Goutam Ghosh
通讯作者：
Choudhury, Goutam Ghosh