scholarly journals Notch signaling suppresses glucose metabolism in mesenchymal progenitors to restrict osteoblast differentiation

2018 ◽  
Vol 128 (12) ◽  
pp. 5573-5586 ◽  
Author(s):  
Seung-Yon Lee ◽  
Fanxin Long
Keyword(s):  
Glucose Metabolism ◽  
Notch Signaling ◽  
Osteoblast Differentiation ◽  
Mesenchymal Progenitors

scholarly journals Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation

2008 ◽  
Vol 14 (3) ◽  
pp. 306-314 ◽  
Author(s):  
Matthew J Hilton ◽  
Xiaolin Tu ◽  
Ximei Wu ◽  
Shuting Bai ◽  
Haibo Zhao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Notch Signaling ◽  
Osteoblast Differentiation ◽  
Mesenchymal Progenitors

scholarly journals CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Regulates Osteoblast Differentiation

2006 ◽  
Vol 26 (16) ◽  
pp. 6105-6116 ◽  
Author(s):  
Ken Shirakawa ◽  
Shingo Maeda ◽  
Tomomi Gotoh ◽  
Makoto Hayashi ◽  
Kenichi Shinomiya ◽  
...  
Keyword(s):  
Osteoblast Differentiation ◽  
Binding Activity ◽  
Bmp Signaling ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Mesenchymal Progenitors ◽  
Homologous Protein ◽  
Dna Binding Activity ◽  
Dominant Negative Inhibitor ◽  
Primary Osteoblasts

ABSTRACT Differentiation of committed osteoblasts is controlled by complex activities involving signal transduction and gene expression, and Runx2 and Osterix function as master regulators for this process. Recently, CCAAT/enhancer-binding proteins (C/EBPs) have been reported to regulate osteogenesis in addition to adipogenesis. However, the roles of C/EBP transcription factors in the control of osteoblast differentiation have yet to be fully elucidated. Here we show that C/EBP homologous protein (CHOP; also known as C/EBPζ) is expressed in bone as well as in mesenchymal progenitors and primary osteoblasts. Overexpression of CHOP reduces alkaline phosphatase activity in primary osteoblasts and suppresses the formation of calcified bone nodules. CHOP-deficient osteoblasts differentiate more strongly than their wild-type counterparts, suggesting that endogenous CHOP plays an important role in the inhibition of osteoblast differentiation. Furthermore, endogenous CHOP induces differentiation of calvarial osteoblasts upon bone morphogenetic protein (BMP) treatment. CHOP forms heterodimers with C/EBPβ and inhibits the DNA-binding activity as well as Runx2-binding activity of C/EBPβ, leading to inhibition of osteocalcin gene transcription. These findings indicate that CHOP acts as a dominant-negative inhibitor of C/EBPβ and prevents osteoblast differentiation but promotes BMP signaling in a cell-type-dependent manner. Thus, endogenous CHOP may have dual roles in regulating osteoblast differentiation and bone formation.

scholarly journals Role of RUNX2 in Melanoma: A New Player in Tumor Progression and Resistance to Therapy

2021 ◽  
Author(s):  
Rachael Pulica ◽  
Cohen Solal Karine ◽  
Ahmed Lasfar
Keyword(s):  
Osteoblast Differentiation ◽  
Skeletal Development ◽  
Critical Role ◽  
Invasion And Metastasis ◽  
Braf Mutations ◽  
Mesenchymal Progenitors ◽  
Oncogenic Pathways ◽  
Cancer Types ◽  
Braf Mutant

RUNX2, a transcription factor, initially known for its indispensable role in skeletal development. RUNX2 is essential for osteoblast differentiation and the maintain of the osteocyte balance. RUNX2 acts directly on osteoblasts via Fgf pathway or on mesenchymal progenitors through Hedgehog, Wnt, Pthlh and DLX5. Currently, many reports point its critical role in the progression and metastasis of several cancer types. RUNX2 is involved in EMT process, invasion and metastasis through the modulation of important oncogenic pathways, including Wnt, FAK/PTK and AKT. In melanoma, RUNX2 is a key player in mediating intrinsic RTK-associated pro-oncogenic properties. We have showed a dramatic up regulation of RUNX2 expression with concomitant up-regulation of EGFR, IGF-1R and AXL, in melanoma cells rendered resistant to BRAF mutant inhibitors. Approximately half of melanomas carry BRAF mutations which enhance tumor invasion and metastasis. In this chapter, we describe the potential mechanisms, leading to the upregulation of RUNX2 in melanoma with BRAF mutations. We also highlight the critical role of PI3K/AKT in the expression and activation of RUNX2, and its consequences on the regulation of many critical factors, controlling cancer invasion and metastasis.

scholarly journals Galectin-3 Inhibits Osteoblast Differentiation through Notch Signaling

Neoplasia ◽  
2014 ◽  
Vol 16 (11) ◽  
pp. 939-949 ◽  
Author(s):  
Kosei Nakajima ◽  
Dhong Hyo Kho ◽  
Takashi Yanagawa ◽  
Yosuke Harazono ◽  
Xiaoge Gao ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Osteoblast Differentiation ◽  
Galectin 3

Canonical Notch signaling is required for bone morphogenetic protein-mediated human osteoblast differentiation

Stem Cells ◽  
2020 ◽  
Author(s):  
Yadav Wagley ◽  
Alessandra Chesi ◽  
Parker K. Acevedo ◽  
Sumei Lu ◽  
Andrew D. Wells ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Bone Morphogenetic Protein ◽  
Osteoblast Differentiation ◽  
Human Osteoblast ◽  
Morphogenetic Protein

scholarly journals Differentiation and Proliferation of Periosteal Osteoblast Progenitors Are Differentially Regulated by Estrogens and Intermittent Parathyroid Hormone Administration

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5713-5723 ◽  
Author(s):  
Mami Ogita ◽  
Marie Therese Rached ◽  
Elzbieta Dworakowski ◽  
John. P. Bilezikian ◽  
Stavroula Kousteni
Keyword(s):  
Osteoblast Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Mesenchymal Progenitors ◽  
Ovariectomized Mice ◽  
Morphogenetic Protein ◽  
Differentiation And Proliferation ◽  
Intermittent Pth ◽  
Osteoblast Progenitors

The periosteum is now widely recognized as a homeostatic and therapeutic target for actions of sex steroids and intermittent PTH administration. The mechanisms by which estrogens suppress but PTH promotes periosteal expansion are not known. In this report, we show that intermittent PTH(1–34) promotes differentiation of periosteal osteoblast precursors as evidenced by the stimulation of the expression or activity of alkaline phosphatase as well as of targets of the bone morphogenetic protein 2 (BMP-2) and Wnt pathways. In contrast, 17β-estradiol (E2) had no effect by itself. However, it attenuated PTH- or BMP-2-induced differentiation of primary periosteal osteoblast progenitors. Administration of intermittent PTH to ovariectomized mice induced rapid phosphorylation of the BMP-2 target Smad1/5/8 in the periosteum. A replacement dose of E2 had no effect by itself but suppressed PTH-induced phosphorylation of Smad1/5/8. In contrast to its effects to stimulate periosteal osteoblast differentiation, PTH promoted and subsequently suppressed proliferation of periosteal osteoblast progenitors in vitro and in vivo. E2 promoted proliferation and attenuated the antiproliferative effect of PTH. Both hormones protected periosteal osteoblasts from apoptosis induced by various proapoptotic agents. These observations suggest that the different effects of PTH and estrogens on the periosteum result from opposing actions on the recruitment of early periosteal osteoblast progenitors. Intermittent PTH promotes osteoblast differentiation from periosteum-derived mesenchymal progenitors through ERK-, BMP-, and Wnt-dependent signaling pathways. Estrogens promote proliferation of early osteoblast progenitors but inhibit their differentiation by osteogenic agents such as PTH or BMP-2.

scholarly journals Gsα enhances commitment of mesenchymal progenitors to the osteoblast lineage but restrains osteoblast differentiation in mice

2011 ◽  
Vol 121 (9) ◽  
pp. 3492-3504 ◽  
Author(s):  
Joy Y. Wu ◽  
Piia Aarnisalo ◽  
Murat Bastepe ◽  
Partha Sinha ◽  
Keertik Fulzele ◽  
...  
Keyword(s):  
Osteoblast Differentiation ◽  
Mesenchymal Progenitors ◽  
Osteoblast Lineage

CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways

2007 ◽  
Vol 354 (2) ◽  
pp. 567-573 ◽  
Author(s):  
Tokutaro Minamizato ◽  
Kei Sakamoto ◽  
Tingjiao Liu ◽  
Hiroki Kokubo ◽  
Ken-ichi Katsube ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Osteoblast Differentiation
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