Background. Achondroplasia (ACH) represents the major cause of dwarfi sm and is due to mutations in the fi broblast growth factor receptor 3 (FGFR3) gene. The cellular mechanisms involved in the reduced growth have been mainly described for in vitro or in vivo models, but few data have been obtained for humans. Methods. Thirteen children with ACH were enrolled in the study; the presence of FGFR3 mutations was determined by restriction fragment length polymorphism analysis and sequencing, whereas protein expression in cartilage biopsy was assessed by immunohistochemistry. Results. Chondrocytes in cartilage biopsies of ACH children were characterized by the presence of growth arrest mediated by STAT activation (both STAT1 and STAT5) and increased expression of p21 and cyclin D1, whereas no expression of either p53 or cyclin D3 could be detected. This mechanism was present in ACH children carrying the G380R mutation but also in a patient in whom no mutation could be detected in the entire coding region of the FGFR3 gene. Conclusions. These data thus demonstrate the presence of a common fi nal mechanism involving p21 and possibly leading to a block in chondrocyte proliferation.

Increased p21 expression in chondrocytes of achondroplasic children independently from the presence of the G380R FGFR3 mutation / A. Parafioriti, S. Del Bianco, D. Barisani, E. Armiraglio, G. Peretti, W. Albisetti. - In: JOURNAL OF ORTHOPAEDIC SCIENCE. - ISSN 0949-2658. - 14:5(2009 Sep), pp. 623-630.

Increased p21 expression in chondrocytes of achondroplasic children independently from the presence of the G380R FGFR3 mutation

G. Peretti
Penultimo
;
W. Albisetti
Ultimo
2009

Abstract

Background. Achondroplasia (ACH) represents the major cause of dwarfi sm and is due to mutations in the fi broblast growth factor receptor 3 (FGFR3) gene. The cellular mechanisms involved in the reduced growth have been mainly described for in vitro or in vivo models, but few data have been obtained for humans. Methods. Thirteen children with ACH were enrolled in the study; the presence of FGFR3 mutations was determined by restriction fragment length polymorphism analysis and sequencing, whereas protein expression in cartilage biopsy was assessed by immunohistochemistry. Results. Chondrocytes in cartilage biopsies of ACH children were characterized by the presence of growth arrest mediated by STAT activation (both STAT1 and STAT5) and increased expression of p21 and cyclin D1, whereas no expression of either p53 or cyclin D3 could be detected. This mechanism was present in ACH children carrying the G380R mutation but also in a patient in whom no mutation could be detected in the entire coding region of the FGFR3 gene. Conclusions. These data thus demonstrate the presence of a common fi nal mechanism involving p21 and possibly leading to a block in chondrocyte proliferation.
Settore MED/33 - Malattie Apparato Locomotore
set-2009
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/209308
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