Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells

Takashi Nakamura, Masahiro Naruse, Yuta Chiba, Toshihisa Komori, Keiichi Sasaki, Masahiro Iwamoto, Satoshi Fukumoto

研究成果: ジャーナルへの寄稿記事

15 引用 (Scopus)

抄録

Hedgehog (Hh) family members are involved in multiple cellular processes including proliferation, migration, differentiation, and cell fate determination. Recently, the novel Hh agonists Hh-Ag 1.3 and 1.7 were identified in a high-throughput screening of small molecule compounds that activate the expression of Gli1, a target of Hh signaling. This study demonstrates that Hh-Ag 1.3 and 1.7 strongly activate the expression of endogenous Gli1 and promote osteoblast differentiation in the mesenchymal stem cell line C3H10T1/2. Both compounds stimulated alkaline phosphatase activity in a dose-dependent manner, and induced osteoblast marker gene expression in C3H10T1/2 cells, which indicated that they had acquired an osteoblast identity. Of the markers, the expression of osterix/Sp7, a downstream target of runt-related transcription factor (Runx)2, was induced by Hh-Ag 1.7, which also rescued the osteoblast differentiation defect of RD-127, a mesenchymal cell line from Runx2-deficient mice. Hh-Ags also activated canonical Wnt signaling and synergized with low doses of BMP-2 to enhance osteoblastic potential. Thus, Hh-Ag 1.7 could be useful for bone healing in individuals with abnormalities in osteogenesis, such as osteoporosis patients and the elderly, and can contribute to the development of novel therapeutics for the treatment of bone fractures and defects.

元の言語英語
ページ(範囲)922-929
ページ数8
ジャーナルJournal of cellular physiology
230
発行部数4
DOI
出版物ステータス出版済み - 4 1 2015

Fingerprint

Hedgehogs
Osteoblasts
Stem cells
Mesenchymal Stromal Cells
Bone
Defects
Gene expression
Alkaline Phosphatase
Screening
Transcription Factors
Cells
Throughput
Cell Line
Molecules
Bone Fractures
Osteogenesis
Osteoporosis
Cell Movement
Cell Differentiation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

これを引用

Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells. / Nakamura, Takashi; Naruse, Masahiro; Chiba, Yuta; Komori, Toshihisa; Sasaki, Keiichi; Iwamoto, Masahiro; Fukumoto, Satoshi.

:: Journal of cellular physiology, 巻 230, 番号 4, 01.04.2015, p. 922-929.

研究成果: ジャーナルへの寄稿記事

Nakamura, T, Naruse, M, Chiba, Y, Komori, T, Sasaki, K, Iwamoto, M & Fukumoto, S 2015, 'Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells', Journal of cellular physiology, 巻. 230, 番号 4, pp. 922-929. https://doi.org/10.1002/jcp.24823
Nakamura T, Naruse M, Chiba Y, Komori T, Sasaki K, Iwamoto M その他. Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells. Journal of cellular physiology. 2015 4 1;230(4):922-929. https://doi.org/10.1002/jcp.24823
Nakamura, Takashi ; Naruse, Masahiro ; Chiba, Yuta ; Komori, Toshihisa ; Sasaki, Keiichi ; Iwamoto, Masahiro ; Fukumoto, Satoshi. / Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells. :: Journal of cellular physiology. 2015 ; 巻 230, 番号 4. pp. 922-929.
@article{9dbd1d74e8ce45339e71e0631d134e4e,
title = "Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells",
abstract = "Hedgehog (Hh) family members are involved in multiple cellular processes including proliferation, migration, differentiation, and cell fate determination. Recently, the novel Hh agonists Hh-Ag 1.3 and 1.7 were identified in a high-throughput screening of small molecule compounds that activate the expression of Gli1, a target of Hh signaling. This study demonstrates that Hh-Ag 1.3 and 1.7 strongly activate the expression of endogenous Gli1 and promote osteoblast differentiation in the mesenchymal stem cell line C3H10T1/2. Both compounds stimulated alkaline phosphatase activity in a dose-dependent manner, and induced osteoblast marker gene expression in C3H10T1/2 cells, which indicated that they had acquired an osteoblast identity. Of the markers, the expression of osterix/Sp7, a downstream target of runt-related transcription factor (Runx)2, was induced by Hh-Ag 1.7, which also rescued the osteoblast differentiation defect of RD-127, a mesenchymal cell line from Runx2-deficient mice. Hh-Ags also activated canonical Wnt signaling and synergized with low doses of BMP-2 to enhance osteoblastic potential. Thus, Hh-Ag 1.7 could be useful for bone healing in individuals with abnormalities in osteogenesis, such as osteoporosis patients and the elderly, and can contribute to the development of novel therapeutics for the treatment of bone fractures and defects.",
author = "Takashi Nakamura and Masahiro Naruse and Yuta Chiba and Toshihisa Komori and Keiichi Sasaki and Masahiro Iwamoto and Satoshi Fukumoto",
year = "2015",
month = "4",
day = "1",
doi = "10.1002/jcp.24823",
language = "English",
volume = "230",
pages = "922--929",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Novel hedgehog agonists promote osteoblast differentiation in mesenchymal stem cells

AU - Nakamura, Takashi

AU - Naruse, Masahiro

AU - Chiba, Yuta

AU - Komori, Toshihisa

AU - Sasaki, Keiichi

AU - Iwamoto, Masahiro

AU - Fukumoto, Satoshi

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Hedgehog (Hh) family members are involved in multiple cellular processes including proliferation, migration, differentiation, and cell fate determination. Recently, the novel Hh agonists Hh-Ag 1.3 and 1.7 were identified in a high-throughput screening of small molecule compounds that activate the expression of Gli1, a target of Hh signaling. This study demonstrates that Hh-Ag 1.3 and 1.7 strongly activate the expression of endogenous Gli1 and promote osteoblast differentiation in the mesenchymal stem cell line C3H10T1/2. Both compounds stimulated alkaline phosphatase activity in a dose-dependent manner, and induced osteoblast marker gene expression in C3H10T1/2 cells, which indicated that they had acquired an osteoblast identity. Of the markers, the expression of osterix/Sp7, a downstream target of runt-related transcription factor (Runx)2, was induced by Hh-Ag 1.7, which also rescued the osteoblast differentiation defect of RD-127, a mesenchymal cell line from Runx2-deficient mice. Hh-Ags also activated canonical Wnt signaling and synergized with low doses of BMP-2 to enhance osteoblastic potential. Thus, Hh-Ag 1.7 could be useful for bone healing in individuals with abnormalities in osteogenesis, such as osteoporosis patients and the elderly, and can contribute to the development of novel therapeutics for the treatment of bone fractures and defects.

AB - Hedgehog (Hh) family members are involved in multiple cellular processes including proliferation, migration, differentiation, and cell fate determination. Recently, the novel Hh agonists Hh-Ag 1.3 and 1.7 were identified in a high-throughput screening of small molecule compounds that activate the expression of Gli1, a target of Hh signaling. This study demonstrates that Hh-Ag 1.3 and 1.7 strongly activate the expression of endogenous Gli1 and promote osteoblast differentiation in the mesenchymal stem cell line C3H10T1/2. Both compounds stimulated alkaline phosphatase activity in a dose-dependent manner, and induced osteoblast marker gene expression in C3H10T1/2 cells, which indicated that they had acquired an osteoblast identity. Of the markers, the expression of osterix/Sp7, a downstream target of runt-related transcription factor (Runx)2, was induced by Hh-Ag 1.7, which also rescued the osteoblast differentiation defect of RD-127, a mesenchymal cell line from Runx2-deficient mice. Hh-Ags also activated canonical Wnt signaling and synergized with low doses of BMP-2 to enhance osteoblastic potential. Thus, Hh-Ag 1.7 could be useful for bone healing in individuals with abnormalities in osteogenesis, such as osteoporosis patients and the elderly, and can contribute to the development of novel therapeutics for the treatment of bone fractures and defects.

UR - http://www.scopus.com/inward/record.url?scp=84919754888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919754888&partnerID=8YFLogxK

U2 - 10.1002/jcp.24823

DO - 10.1002/jcp.24823

M3 - Article

C2 - 25215620

AN - SCOPUS:84919754888

VL - 230

SP - 922

EP - 929

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 4

ER -