NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia.
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.
Yu
Chunying
C
Program in Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.
Le
Anh-Thy
AT
Yeger
Herman
H
Perbal
Bernard
B
Alman
Benjamin A
BA
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D055511:CCN Intercellular Signaling Proteins; D002357:Cartilage Diseases / Q000235:genetics* / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D002812:Chondroma / Q000235:genetics / Q000473:pathology; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology; D055513:Connective Tissue Growth Factor; D003470:Culture Media; D055515:Cysteine-Rich Protein 61; D005269:Femur; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006132:Growth Plate / Q000502:physiology*; D006801:Humans; D006984:Hypertrophy; D017874:Immediate-Early Proteins / Q000032:analysis* / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000032:analysis*; D055514:Nephroblastoma Overexpressed Protein; D015513:Oncogene Proteins / Q000235:genetics; D009924:Organ Culture Techniques; D044162:Parathyroid Hormone-Related Protein; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins
D055511:CCN Intercellular Signaling Proteins; C501848:CCN1 protein, human; C491850:CCN1 protein, mouse; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C526319:CCN3 protein, human; C116396:CCN4 protein, human; C492067:CCN4 protein, mouse; C526320:Ccn3 protein, mouse; D003470:Culture Media; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008934:Mitogens; D055514:Nephroblastoma Overexpressed Protein; D015513:Oncogene Proteins; D044162:Parathyroid Hormone-Related Protein; D011518:Proto-Oncogene Proteins; D055513:Connective Tissue Growth Factor