单羧酸转运蛋白 1 通过抑制骨细胞分化的负调控因子 p53 促进成骨细胞分化。
Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.
机构信息
Departments of Biochemistry, Showa University School of Dentistry, Tokyo, Japan.
Departments of Periodontology, Showa University School of Dentistry, Tokyo, Japan.
出版信息
Sci Rep. 2018 Jul 12;8(1):10579. doi: 10.1038/s41598-018-28605-5.
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.
单羧酸转运蛋白-1（MCT-1）是一种用于转运单羧酸的跨膜转运蛋白，包括乳酸盐和丙酮酸。用其小干扰 RNA（siRNA）沉默 Mct1 可抑制 BMP-2 诱导的小鼠成肌细胞 C2C12 中骨分化标志物基因 Tnap、Runx2 和 Sp7 的表达。Mct1 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，Mct1 siRNA 对 BMP-2 刺激的 C2C12 细胞中的 Smad1/5 或 ERK/JNK 通路没有影响，但以 BMP-2 非依赖性方式上调 C2C12 细胞中 p53（Trp53）的 mRNA 表达并使 p53 核内积累。C2C12 细胞中 Mct1 siRNA 对成骨细胞分化的抑制作用被 Trp53 siRNA 的共转染所消除。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。
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