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Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation.

Publication ,  Journal Article
Zhang, H; Sun, W; Li, X; Wang, M; Boyce, BF; Hilton, MJ; Xing, L
Published in: Bone
September 2016

Notch signaling plays a critical role in maintaining bone homeostasis partially by controlling the formation of osteoblasts from mesenchymal stem cells (MSCs). We reported that TNF activates Notch signaling in MSCs which inhibits osteoblast differentiation in TNF transgenic (TNF-Tg) mice, a mouse model of chronic inflammatory arthritis. In the current study, we used Hes1-GFP and Hes1-GFP/TNF-Tg mice to study the distribution and dynamic change of Notch active cells in normal and inflammatory bone loss and mechanisms mediating their enhanced proliferation. We found that Hes1-GFP+ cells are composed of cells expressing mesenchymal, hematopoietic and endothelial surface markers. CD45-/Hes1-GFP+ cells express high levels of mesenchymal markers and form CFU-F and CFU-ALP colonies. Expansion of CFU-F colonies is associated with a rapid increase in Hes1-GFP+ cell numbers and their GFP intensity. The GFP signal is lost when a CFU-F colony differentiates into an ALP+ osteoblast colony. TNF increases the numbers of CD45-/Hes1-GFP+ cells, which are stained negatively for osteoblast marker osteocalcin and localized adjacent to endosteal and trabecular bone surfaces. CD45-/Hes1-GFP+ cells in Hes1-GFP/TNF-Tg mice have increased BrdU incorporation and PDGFRβ levels. TNF increases the number of proliferating Hes1-GFP+ cells, which is prevented by a specific PDGFRβ inhibitor. Notch inhibition blocks TNF-mediated PDGFRβ expression and cell proliferation. Thus, TNF-induced MSC proliferation is mediated by PDGFRβ signal, which works at downstream of Notch. Hes1-GFP mice can be used to assess the activation status of Notch in bone cells.

Duke Scholars

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Published In

Bone

DOI

EISSN

1873-2763

Publication Date

September 2016

Volume

90

Start / End Page

80 / 89

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Receptors, Notch
  • Receptor, Platelet-Derived Growth Factor beta
  • Promoter Regions, Genetic
  • Osteoblasts
  • Mice, Transgenic
  • Mesenchymal Stem Cells
  • Leukocyte Common Antigens
  • Inflammation
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, H., Sun, W., Li, X., Wang, M., Boyce, B. F., Hilton, M. J., & Xing, L. (2016). Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation. Bone, 90, 80–89. https://doi.org/10.1016/j.bone.2016.06.003
Zhang, Hengwei, Wen Sun, Xing Li, Mengmeng Wang, Brendan F. Boyce, Matthew J. Hilton, and Lianping Xing. “Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation.Bone 90 (September 2016): 80–89. https://doi.org/10.1016/j.bone.2016.06.003.
Zhang H, Sun W, Li X, Wang M, Boyce BF, Hilton MJ, et al. Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation. Bone. 2016 Sep;90:80–9.
Zhang, Hengwei, et al. “Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation.Bone, vol. 90, Sept. 2016, pp. 80–89. Pubmed, doi:10.1016/j.bone.2016.06.003.
Zhang H, Sun W, Li X, Wang M, Boyce BF, Hilton MJ, Xing L. Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation. Bone. 2016 Sep;90:80–89.

Published In

Bone

DOI

EISSN

1873-2763

Publication Date

September 2016

Volume

90

Start / End Page

80 / 89

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Receptors, Notch
  • Receptor, Platelet-Derived Growth Factor beta
  • Promoter Regions, Genetic
  • Osteoblasts
  • Mice, Transgenic
  • Mesenchymal Stem Cells
  • Leukocyte Common Antigens
  • Inflammation
  • Humans