Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.
Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.
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DOI：
10.1038/s41598-018-28605-5
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发表时间：
2018-07-12
影响因子：
4.6
通讯作者：
Kamijo R
中科院分区：
文献类型：
--
作者：
Sasa K;Yoshimura K;Yamada A;Suzuki D;Miyamoto Y;Imai H;Nagayama K;Maki K;Yamamoto M;Kamijo R
单羧酸转运蛋白-1（MCT-1）是一种跨膜转运单羧酸的蛋白，包括乳酸和丙酮酸。沉默Mct 1的小干扰RNA（siRNA）抑制成骨细胞分化的标记基因，即Tnap，Runx 2和Sp 7的表达，诱导BMP-2在小鼠成肌细胞C2 C12细胞。Mct 1 siRNA还抑制碱性磷酸酶活性，以及小鼠原代成骨细胞中Tnap和Bglap mRNA的表达。另一方面，Mct 1 siRNA对BMP-2刺激的C2 C12细胞中的Smad 1/5或ERK/JNK通路没有影响，但它以不依赖于BMP-2的方式上调C2 C12细胞中p53（Trp 53）的mRNA表达以及p53的核积聚。共转染Trp 53 siRNA可消除Mct 1 siRNA对C2 C12细胞成骨细胞分化的抑制作用。总之，这些结果表明MCT-1通过抑制p53作为成骨细胞分化的正调节剂发挥作用。
Monocarboxylate transporter-1 (MCT-1) is a transmembrane transporter for monocarboxylates including lactate and pyruvate. Silencing Mct1 by its small interfering RNA (siRNA) suppressed the expression of marker genes for osteoblast differentiation, namely, Tnap, Runx2, and Sp7, induced by BMP-2 in mouse myoblastic C2C12 cells. Mct1 siRNA also suppressed alkaline phosphatase activity, as well as expressions of Tnap and Bglap mRNAs in mouse primary osteoblasts. On the other hand, Mct1 siRNA did not have effects on the Smad1/5 or ERK/JNK pathways in BMP-2-stimulated C2C12 cells, while it up-regulated the mRNA expression of p53 (Trp53) as well as nuclear accumulation of p53 in C2C12 cells in a BMP-2-independent manner. Suppression of osteoblastic differentiation by Mct1 siRNA in C2C12 cells was abolished by co-transfection of Trp53 siRNA. Together, these results suggest that MCT-1 functions as a positive regulator of osteoblast differentiation via suppression of p53.
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DOI：
10.1083/jcb.200610046
发表时间：
2007-02-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
通讯作者：
Franceschi RT
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
4.8
作者：
Sang, NL;Stiehl, DP;Caro, J
通讯作者：
Caro, J
影响因子：
12.7
作者：
Rahman, Md Shaifur;Akhtar, Naznin;Jamil, Hossen Mohammad;Banik, Rajat Suvra;Asaduzzaman, Sikder M.
通讯作者：
Asaduzzaman, Sikder M.
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Tanabe, Koji;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya