The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation.

By K. Nakashima, Xin Zhou, G. Kunkel, Zhaoping Zhang, J. Deng, R. Behringer, Benoit de Crombrugghe. Cell, 2002

3,455 citations recorded by the source corpus.

We have identified a novel zinc finger-containing transcription factor, called Osterix (Osx), that is specifically expressed in all developing bones. In Osx null mice, no bone formation occurs. In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix. However, the mesenchymal cells do not deposit bone matrix. Similarly, cells in the periosteum and in the condensed mesenchyme of membranous skeletal elements cannot differentiate into osteoblasts. These cells do, however, express Runx2/Cbfa1, another transcription factor required for bone formation. In contrast, Osx is not expressed in Runx2/Cbfa1 null mice. Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/caf75127f6aefa148a0e1fca993f8d8714ae6005

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In Molecular Biology

1. Fanxin Long
2. D. Ornitz
3. T. Komori
4. J. Smolen
5. K. Redlich
6. L. Xing
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In Oncology

1. J. Smolen
2. K. Redlich
3. S. Shi
4. S. Gronthos
5. Fanxin Long
6. M. Zaidi
7. T. Suda
8. E. Eriksen

Citations in the corpus

• Effects of dexamethasone, ascorbic acid and β-glycerophosphate on the osteogenic differentiation of stem cells in vitro (2013, background): “These Smads form complexes with Smad4 and translocate into the nucleus where they regulate gene expression of the osteogenic transcription factors Runx2, osterix and the MSX/DLX homeodomain proteins [24-26], as well as transcriptional co-activators such as p300, CBP and P/CAF [27-29].”
• Inflammatory bone loss: pathogenesis and therapeutic intervention (2012, background): “Osterix-deficient animals do not form bone despite having normal levels of RUNX2 (Ref”
• Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? (2016, background): “Runx2 and Osterix are considered as master transcription factors in regulating osteogenic differentiation of MSCs.(88,89)”
• Development of the endochondral skeleton. (2013, background): “Deletion of OSX results in a complete absence of osteoblasts in the mouse embryo, even though expression of RUNX2 is relatively normal (Nakashima et al. 2002).”
• Biology of RANK, RANKL, and osteoprotegerin (2007, background): “The likely explanation for this effect of cyclosporine A is that NFATc1 also positively regulates expression of osterix, an essential transcription factor that regulates osteoblast function [42], and the net effect is reduced bone formation and osteoporosis [43].”
• Cellular mechanisms of bone remodeling (2010, background): “Osterix is another transcription factor essential for osteoblast differentiation [11].”
• Osteoblasts in prostate cancer metastasis to bone (2005, background): “Another transcription factor that controls osteogenesis is osteri”
• Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation (2014, background): “Osx is expressed in prehypertrophic chondrocytes and osteoblasts and is essential for preosteoblast differentiation (9): it directly transactivates Col1a1, which encodes collagen I, a marker of differentiated osteoblasts.”
• Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors (2006, background): “Hence, there is a complete loss of bone deposition that is reminiscent of the loss of osteoblast determinants, such as Runx2 (Komori et al., 1997; Ducy et al., 1997; Otto et al., 1997) and Osx1 (Nakashima et al., 2002).”
• Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow (2003, background): “…precursors was provided by the pioneering studies of Friedenstein and colleagues, who demonstrated the in vitro growth of adherent colonies of cells morphologically resembling fibroblasts (CFU-F) derived from explants of BM (Castro-Malaspina et al., 1980; Friedenstein et al., 1970; Owen, 1988).”
• Genetic Analysis of the Roles of BMP2, BMP4, and BMP7 in Limb Patterning and Skeletogenesis (2006, background): “The (35)S-labeled cRNA probes were transcribed from plasmids encoding type I collagen [59], runx2 [60], osteopontin [61], and osterix [46].”
• Transforming Growth Factor- 1 to the Bone (2005, background): “In addition, several other transcription factors and homeobox proteins, such as Dlx5, Msx2, Bapx1, Hoxa-2, Osx, and AP-1, affect osteoblast differentiation (102, 104).”