title: The monocarboxylate transporter 8 and L-type amino acid transporters 1 and 2 are expressed in mouse skeletons and in osteoblastic MC3T3-E1 cells.
abstract: BACKGROUND
  Several plasma membrane transporters have been shown to mediate the cellular influx and/or efflux of iodothyronines, including the sodium-independent organic anion co-transporting polypeptide 1 (OATP1), the sodium taurocholate co-transporting polypeptide (NTCP), the L-type amino acid transporter 1 (LAT1) and 2 (LAT2), and the monocarboxylate transporter 8 (MCT8). The aim of this study was to investigate if the mRNAs of these transporters were expressed and regulated by thyroid hormone (TH) in mouse calvaria-derived osteoblastic MC3T3-E1 cells and in the fetal and postnatal bones of mice.
  
  
  METHODS
  The mRNA expression of the iodothyronine transporters was investigated with real-time polymerase chain reaction analysis in euthyroid and hypothyroid fetuses and litters of mice and in MC3T3-E1 cells treated with increasing doses of triiodothyronine (T(3); 10(-10) to 10(-6) M) or with 10(-8) M T(3) for 1-9 days.
  
  
  RESULTS
  MCT8, LAT1, and LAT2 mRNAs were detected in fetal and postnatal femurs and in MC3T3-E1 cells, while OATP1 and NTCP mRNAs were not. LAT1 and LAT2 mRNAs were not affected by TH status in vivo or in vitro or by the stage of bone development or osteoblast maturation (analyzed by the expression of osteocalcin and alkaline phosphatase, which are key markers of osteoblastic differentiation). In contrast, the femoral mRNA expression of MCT8 decreased significantly during post-natal development, whereas MCT8 mRNA expression increased as MC3T3-E1 cells differentiated. We also showed that MCT8 mRNA was up-regulated in the femur of hypothyroid animals, and that it was down-regulated by treatment with T(3) in MC3T3-E1 cells.
  
  
  CONCLUSIONS
  This is the first study to demonstrate the mRNA expression of LAT1, LAT2, and MCT8 in the bone tissue of mice and in osteoblast-like cells. In addition, the pattern of MCT8 expression observed in vivo and in vitro suggests that MCT8 may be important to modulate TH effects on osteoblast differentiation and on bone development and metabolism.
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Luciane P
authors.initials: LP
authors.lastname: Capelo
authors.forename: Eduardo H
authors.initials: EH
authors.lastname: Beber
authors.forename: Tatiana L
authors.initials: TL
authors.lastname: Fonseca
authors.forename: Cecilia H A
authors.initials: CH
authors.lastname: Gouveia
mesh_terms: D027182:Amino Acid Transport System y+ / Q000096:biosynthesis*; D027241:Amino Acid Transport System y+L; D000818:Animals; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D005269:Femur / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D027301:Fusion Regulatory Protein 1, Light Chains / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D007037:Hypothyroidism / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D051379:Mice; D027501:Monocarboxylic Acid Transporters; D010006:Osteoblasts / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D027981:Symporters; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D027182:Amino Acid Transport System y+; D027241:Amino Acid Transport System y+L; D027301:Fusion Regulatory Protein 1, Light Chains; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C518286:SLC7A8 protein, mouse; C484257:Slc16a2 protein, mouse; C518287:Slc7a7 protein, mouse; D027981:Symporters; D014284:Triiodothyronine; D013974:Thyroxine