title: Role of C-type natriuretic peptide signalling in maintaining cartilage and bone function.
abstract: C-type natriuretic peptide (CNP) has been demonstrated in human and mouse models to play critical roles in cartilage homeostasis and endochondral bone formation. Indeed, targeted inactivation of the genes encoding CNP results in severe dwarfism and skeletal defects with a reduction in growth plate chondrocytes. Conversely, cartilage-specific overexpression of CNP was observed to rescue the phenotype of CNP deficient mice and significantly enhanced bone growth caused by growth plate expansion. In vitro studies reported that exogenous CNP influenced chondrocyte differentiation, proliferation and matrix synthesis with the response dependent on CNP concentration. The chondroprotective effects were shown to be mediated by natriuretic peptide receptor (Npr)2 and enhanced synthesis of cyclic guanosine-3',5'-monophosphate (cGMP) production. Recent studies also showed certain homeostatic effects of CNP are mediated by the clearance inactivation receptor, Npr3, highlighting several mechanisms in maintaining tissue homeostasis. However, the CNP signalling systems are complex and influenced by multiple factors that will lead to altered signalling and tissue dysfunction. This review will discuss the differential role of CNP signalling in regulating cartilage and bone homeostasis and how the pathways are influenced by age, inflammation or sex. Evidence indicates that enhanced CNP signalling may prevent growth retardation and protect cartilage in patients with inflammatory joint disease.
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Peake
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hobbs
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: B
authors.initials: B
authors.lastname: Pingguan-Murphy
authors.affiliation: Centre for Genomics and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crew Road, Edinburgh EH4 2XU, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Salter
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Paris 06, INSERM UMRS 938, Assistance Publique-Hopitaux de Paris, Department of Rheumatology and DHU i2B, Hôpital Saint-Antoine, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Berenbaum
authors.affiliation: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Electronic address: t.t.chowdhury@qmul.ac.uk.
authors.forename: T T
authors.initials: TT
authors.lastname: Chowdhury
mesh_terms: D000818:Animals; D001846:Bone Development; D002356:Cartilage / Q000254:growth & development* / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D020098:Natriuretic Peptide, C-Type / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*
chemical_list: D020098:Natriuretic Peptide, C-Type
keywords: C-type natriuretic peptide; Cartilage homeostasis; Inflammation; Natriuretic peptide receptor; Osteoarthritis