Expression of TLE3 by bone marrow stromal cells is regulated by canonical Wnt signaling.
Transducing-like enhancer of split 3 (TLE3), one of the Groucho/TLE family members, targets Runx2 transcription and suppresses osteoblast differentiation in bone marrow stromal cells (BMSCs). Here, we identify Wnt responsive elements of the TLE3 promoter region through comparative genomic and functional analyses and show that expression of TLE3 is increased by Wnt signaling, which is important for osteoblast differentiation. We also demonstrated that TLE3 is able to suppress canonical Wnt signaling in BMSCs. Taken together, our data suggest that induction of TLE3 by Wnt signaling is part of a negative feedback loop active during osteoblast differentiation.
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan; Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA. Electronic address: kokabu2@saitama-med.ac.jp.
Shoichiro
S
Kokabu
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Tsuyoshi
T
Sato
Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
Satoshi
S
Ohte
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Yuichiro
Y
Enoki
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Masahiko
M
Okubo
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Naoki
N
Hayashi
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Junya
J
Nojima
Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
Sho
S
Tsukamoto
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Yosuke
Y
Fukushima
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Yasuaki
Y
Sakata
Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
Takenobu
T
Katagiri
Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
Vicki
V
Rosen
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Saitama 350-0495, Japan.
Tetsuya
T
Yoda
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D056970:Co-Repressor Proteins / Q000235:genetics*; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D056970:Co-Repressor Proteins; C570667:TLE3 protein, human; C104849:Tle3 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin
Co-repressor; Groucho; Osteoblastogenesis; Osteoporosis; Transducing-like enhancer of split; Wnt