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Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.


ABSTRACT: 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.

SUBMITTER: Sasa K 

PROVIDER: S-EPMC6043614 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.

Sasa Kiyohito K   Yoshimura Kentaro K   Yamada Atsushi A   Suzuki Dai D   Miyamoto Yoichi Y   Imai Hiroko H   Nagayama Kazuhiro K   Maki Koutaro K   Yamamoto Matsuo M   Kamijo Ryutaro R  

Scientific reports 20180712 1


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  ...[more]

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