title: C-type natriuretic peptide signalling drives homeostatic effects in human chondrocytes.
abstract: Signals induced by mechanical loading and C-type natriuretic peptide (CNP) represent chondroprotective routes that may potentially prevent osteoarthritis (OA). We examined whether CNP will reduce hyaluronan production and export via members of the multidrug resistance protein (MRP) and diminish pro-inflammatory effects in human chondrocytes. The presence of interleukin-1β (IL-1β) increased HA production and export via MRP5 that was reduced with CNP and/or loading. Treatment with IL-1β conditioned medium increased production of catabolic mediators and the response was reduced with the hyaluronan inhibitor, Pep-1. The induction of pro-inflammatory cytokines by the conditioned medium was reduced by CNP and/or Pep-1, αCD44 or αTLR4 in a cytokine-dependent manner, suggesting that the CNP pathway is protective and should be exploited further.
authors: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors: N J
authors: NJ
authors: Peake
authors: Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors: D L
authors: DL
authors: Bader
authors: National Institute for Biological Standards and Control, Biotherapeutics Group, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
authors: S
authors: S
authors: Vessillier
authors: Department of Orthopaedics and Trauma, The Royal London Hospital and Barts & The London School of Medicine & Dentistry, Queen Mary University of London, Whitechapel Road, London E1 1BB, UK.
authors: M
authors: M
authors: Ramachandran
authors: Centre for Genomics and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crew Road, Edinburgh EH4 2XU, UK.
authors: D M
authors: DM
authors: Salter
authors: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, QMUL, Charterhouse Square, London EC1M 6BQ, UK.
authors: A J
authors: AJ
authors: Hobbs
authors: 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: T T
authors: TT
authors: Chowdhury
mesh_terms: D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D017077:Culture Media, Conditioned; D006152:Cyclic GMP / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008954:Models, Biological; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017077:Culture Media, Conditioned; D006152:Cyclic GMP; D016207:Cytokines; D006820:Hyaluronic Acid; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020098:Natriuretic Peptide, C-Type; D010455:Peptides; C073492:ABCC4 protein, human; C120809:ABCC5 protein, human; C575521:glycyl-alanyl-histidyl-tryptophyl-glutaminyl-phenylalanyl-asparagyl-alanyl-leucyl-threonyl-valyl-arginine
keywords: C-type natriuretic peptide; Chondrocyte; Interleukin-1β; Mechanical loading; Osteoarthritis