Expression of master regulatory genes controlling skeletal development in benign cartilage and bone forming tumors.

Recent progress in skeletal molecular biology has led to the clarification of the transcriptional mechanisms of chondroblastic and osteoblastic lineage differentiation. Three master transcription factors-Sox9, Runx2, and Osterix-were shown to play an essential role in determining the skeletal progenitor cells' fate. The present study evaluates the expression of these factors in 4 types of benign bone tumors-chondromyxoid fibroma, chondroblastoma, osteoid osteoma, and osteoblastoma-using immunohistochemistry and tissue microarrays. Osteoid osteoma and osteoblastoma showed strong nuclear expression of Osterix and Runx2. In contrast, only a few chondroblastomas showed positive nuclear expression of Osterix. Strong nuclear expression of Sox9 was detected in all chondroblastomas, whereas nearly half of the osteoblastomas showed focal weak cytoplasmic expression of Sox9.

[1]  Hai-sheng Li,et al.  Molecular mechanism of osteochondroprogenitor fate determination during bone formation. , 2006, Advances in experimental medicine and biology.

[2]  E. Schwarz,et al.  Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. , 2006, Gene.

[3]  Mutation analysis of SOX9 and single copy number variant analysis of the upstream region in eight patients with campomelic dysplasia and acampomelic campomelic dysplasia , 2009, American journal of medical genetics. Part A.

[4]  R. Fukuyama,et al.  Induction of Osteoclast Differentiation by Runx2 through Receptor Activator of Nuclear Factor-κB Ligand (RANKL) and Osteoprotegerin Regulation and Partial Rescue of Osteoclastogenesis in Runx2–/– Mice by RANKL Transgene* , 2003, Journal of Biological Chemistry.

[5]  Hye-Rim Park,et al.  Prognostic Implication of Immunohistochemical Runx2 Expression in Osteosarcoma , 2009, Tumori.

[6]  E. Schwarz,et al.  Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis , 2008, Oncogene.

[7]  G. Karsenty.  Transcriptional control of skeletogenesis. , 2008, Annual review of genomics and human genetics.

[8]  H. Nagatsuka,et al.  Immunohistochemical examination of cytological differentiation in osteosarcomas. , 2005, European journal of medical research.

[9]  J. Deng,et al.  Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Baggerly,et al.  Alterations in transcription clusters underlie development of bladder cancer along papillary and nonpapillary pathways , 2005, Laboratory Investigation.

[11]  Hye-Rim Park,et al.  Differential expression of Runx2 and Indian hedgehog in cartilaginous tumors , 2008, Pathology & Oncology Research.

[12]  J. Deng,et al.  The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation , 2002, Cell.

[13]  T. Komori.  Requisite roles of Runx2 and Cbfb in skeletal development , 2003, Journal of Bone and Mineral Metabolism.

[14]  E. Cameron,et al.  Conservation and expression of an alternative 3' exon of Runx2 encoding a novel proline-rich C-terminal domain. , 2004, Gene.

[15]  T. Kodama,et al.  NFAT and Osterix cooperatively regulate bone formation , 2005, Nature Medicine.

[16]  B. de Crombrugghe,et al.  Positive Regulation of Adult Bone Formation by Osteoblast‐Specific Transcription Factor Osterix , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  Véronique Lefebvre,et al.  A new long form of Sox5 (L‐Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene , 1998, The EMBO journal.

[18]  S. Ranganathan,et al.  Functional and Structural Studies of Wild Type SOX9 and Mutations Causing Campomelic Dysplasia* , 1999, The Journal of Biological Chemistry.

[19]  S. Takeda,et al.  Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice. , 2001, Genes & development.

[20]  E. Kleinerman,et al.  Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma. , 2005, Cancer research.

[21]  Richard R. Behringer,et al.  Sox9 is required for cartilage formation , 1999, Nature Genetics.

[22]  B. Czerniak,et al.  Sox9, a master regulator of chondrogenesis, distinguishes mesenchymal chondrosarcoma from other small blue round cell tumors. , 2003, Human pathology.

[23]  A. Yanagisawa,et al.  Immunohistochemical analysis for Sox9 reveals the cartilaginous character of chondroblastoma and chondromyxoid fibroma of the bone. , 2010, Human pathology.

[24]  K. Nakashima,et al.  Transcriptional mechanisms in osteoblast differentiation and bone formation. , 2003, Trends in genetics : TIG.

[25]  E. Kleinerman,et al.  The Osterix Transcription Factor Down-Regulates Interleukin-1α Expression in Mouse Osteosarcoma Cells , 2008, Molecular Cancer Research.

[26]  David M. Thomas,et al.  Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma , 2004, The Journal of cell biology.

[27]  C. Lengner,et al.  Networks and hubs for the transcriptional control of osteoblastogenesis , 2006, Reviews in Endocrine and Metabolic Disorders.

[28]  P N Goodfellow,et al.  SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene , 1997, Molecular and cellular biology.

[29]  R. Behringer,et al.  Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondrium. , 2006, Genes & development.