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Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway
- Source :
- Nature Medicine. 10:80-86
- Publication Year :
- 2003
- Publisher :
- Springer Science and Business Media LLC, 2003.
-
Abstract
- Achondroplasia is the most common genetic form of human dwarfism, for which there is presently no effective therapy. C-type natriuretic peptide (CNP) is a newly identified molecule that regulates endochondral bone growth through GC-B, a subtype of particulate guanylyl cyclase. Here we show that targeted overexpression of CNP in chondrocytes counteracts dwarfism in a mouse model of achondroplasia with activated fibroblast growth factor receptor 3 (FGFR-3) in the cartilage. CNP prevented the shortening of achondroplastic bones by correcting the decreased extracellular matrix synthesis in the growth plate through inhibition of the MAPK pathway of FGF signaling. CNP had no effect on the STAT-1 pathway of FGF signaling that mediates the decreased proliferation and the delayed differentiation of achondroplastic chondrocytes. These results demonstrate that activation of the CNP-GC-B system in endochondral bone formation constitutes a new therapeutic strategy for human achondroplasia.
- Subjects :
- musculoskeletal diseases
MAPK/ERK pathway
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
MAP Kinase Signaling System
Cellular differentiation
Dwarfism
Mice, Transgenic
Biology
Fibroblast growth factor
General Biochemistry, Genetics and Molecular Biology
Achondroplasia
Mice
Chondrocytes
Organ Culture Techniques
Internal medicine
medicine
Animals
Receptor, Fibroblast Growth Factor, Type 3
RNA, Messenger
Transgenes
Cartilage
Cell Differentiation
Natriuretic Peptide, C-Type
General Medicine
Protein-Tyrosine Kinases
Fibroblast growth factor receptor 3
medicine.disease
Receptors, Fibroblast Growth Factor
Endochondral bone growth
Cell biology
Fibroblast Growth Factors
Phenotype
medicine.anatomical_structure
Endocrinology
Cell Division
Subjects
Details
- ISSN :
- 1546170X and 10788956
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Medicine
- Accession number :
- edsair.doi.dedup.....7e58445112d51a98777ab7bd0878566b