Abstract
Growth plate chondrocytes undergo a coordinated differentiation process resulting in terminal differentiation and new bone formation. Enchondromas are pre-malignant, benign cartilaginous lesions that arise from growth plate chondrocytes that fail to undergo terminal differentiation. NOV (nephroblastoma overexpressed) is a member of the CCN family of proteins, which share a common multi-modular organization. While the role of NOV in chondrocyte development and cartilage neoplasia is not known, other CCN family members play a role in chondrocyte differentiation, or are differentially regulated in cartilage neoplasia. In embryonic murine growth plates, NOV was expressed in pre-hypertrophic and early hypertrophic chondrocytes. PTHrP treatment (which inhibits terminal differentiation) decreased NOV expression in murine femurs maintained in organ culture, and decreased the activity of a NOV reporter construct in vitro. Expression of the CCN family members NOV, CTGF, CYR61, and WISP-1 was examined in 15 chondrosarcomas of various grades and in three enchondromas. Expression of all of the family members was lower in the higher-grade tumours. As identification of the grade of cartilage neoplasia can sometimes be difficult using histology alone, the level of expression of CCN family members could be a useful adjunct in the determination of tumour grade.
Copyright 2003 John Wiley & Sons, Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Neoplasms / genetics*
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Bone Neoplasms / pathology
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CCN Intercellular Signaling Proteins
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Cartilage Diseases / genetics*
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Cartilage Diseases / pathology
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Chondrocytes / pathology
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Chondroma / genetics
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Chondroma / pathology
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Chondrosarcoma / genetics*
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Chondrosarcoma / pathology
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Connective Tissue Growth Factor
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Culture Media
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Cysteine-Rich Protein 61
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Femur
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Gene Expression Regulation, Neoplastic / genetics
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Growth Plate / physiology*
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Humans
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Hypertrophy
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Immediate-Early Proteins / analysis*
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Immediate-Early Proteins / genetics
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Immunohistochemistry / methods
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Intercellular Signaling Peptides and Proteins / analysis*
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Intercellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins
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Mice
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Mice, Inbred Strains
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Mitogens / analysis*
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Nephroblastoma Overexpressed Protein
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Oncogene Proteins / genetics
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Organ Culture Techniques
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Parathyroid Hormone-Related Protein
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Polymerase Chain Reaction / methods
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins
Substances
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CCN Intercellular Signaling Proteins
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CCN1 protein, human
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CCN1 protein, mouse
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CCN2 protein, human
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CCN2 protein, mouse
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CCN3 protein, human
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CCN4 protein, human
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CCN4 protein, mouse
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Ccn3 protein, mouse
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Culture Media
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Cysteine-Rich Protein 61
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Immediate-Early Proteins
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Mitogens
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Nephroblastoma Overexpressed Protein
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Oncogene Proteins
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Parathyroid Hormone-Related Protein
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Proto-Oncogene Proteins
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Connective Tissue Growth Factor