RRC ID 54029
Author Sasa K, Yoshimura K, Yamada A, Suzuki D, Miyamoto Y, Imai H, Nagayama K, Maki K, Yamamoto M, Kamijo R.
Title Monocarboxylate transporter-1 promotes osteoblast differentiation via suppression of p53, a negative regulator of osteoblast differentiation.
Journal Sci Rep
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.
Volume 8(1)
Pages 10579
Published 2018-7-12
DOI 10.1038/s41598-018-28605-5
PII 10.1038/s41598-018-28605-5
PMID 30002387
PMC PMC6043614
MeSH Animals Bone Morphogenetic Protein 2 / genetics Bone Morphogenetic Protein 2 / metabolism Cell Differentiation* Cell Line Gene Knockdown Techniques Mice Monocarboxylic Acid Transporters / genetics Monocarboxylic Acid Transporters / metabolism* Myoblasts / physiology* Osteoblasts / physiology* Primary Cell Culture RNA, Small Interfering / metabolism Recombinant Proteins / genetics Recombinant Proteins / metabolism Symporters / genetics Symporters / metabolism* Tumor Suppressor Protein p53 / metabolism*
IF 3.998
Times Cited 4
Human and Animal Cells C2C12(RCB0987)