title: In vitro models for the study of osteoarthritis.
abstract: Osteoarthritis (OA) is a prevalent disease of most mammalian species and is a significant cause of welfare and economic morbidity in affected individuals and populations. In vitro models of osteoarthritis are vital to advance research into the causes of the disease, and the subsequent design and testing of potential therapeutics. However, a plethora of in vitro models have been used by researchers but with no consensus on the most appropriate model. Models attempt to mimic factors and conditions which initiate OA, or dissect the pathways active in the disease. Underlying uncertainty as to the cause of OA and the different attributes of isolated cells and tissues used mean that similar models may produce differing results and can differ from the naturally occurring disease. This review article assesses a selection of the in vitro models currently used in OA research, and considers the merits of each. Particular focus is placed on the more prevalent cytokine stimulation and load-based models. A brief review of the mechanism of these models is given, with their relevance to the naturally occurring disease. Most in vitro models have used supraphysiological loads or cytokine concentrations (compared with the natural disease) in order to impart a timely response from the cells or tissue assessed. Whilst models inducing OA-like pathology with a single stimulus can answer important biological questions about the behaviour of cells and tissues, the development of combinatorial models encompassing different physiological and molecular aspects of the disease should more accurately reflect the pathogenesis of the naturally occurring disease.
authors.affiliation: The Roslin Institute and the Royal (Dick) School of Veterinary Studies, Division of Veterinary Clinical Sciences, The University of Edinburgh, Easter Bush Veterinary Centre, Edinburgh EH25 9RG, UK. Electronic address: craig.johnson@roslin.ed.ac.uk.
authors.forename: Craig I
authors.initials: CI
authors.lastname: Johnson
authors.affiliation: The Roslin Institute and the Royal (Dick) School of Veterinary Studies, Division of Veterinary Clinical Sciences, The University of Edinburgh, Easter Bush Veterinary Centre, Edinburgh EH25 9RG, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Argyle
authors.affiliation: The Roslin Institute and the Royal (Dick) School of Veterinary Studies, Division of Veterinary Clinical Sciences, The University of Edinburgh, Easter Bush Veterinary Centre, Edinburgh EH25 9RG, UK.
authors.forename: Dylan N
authors.initials: DN
authors.lastname: Clements
mesh_terms: D000818:Animals; D000829:Animals, Domestic; D001696:Biomechanical Phenomena; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D066298:In Vitro Techniques / Q000379:methods*; D010003:Osteoarthritis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*
chemical_list: D016207:Cytokines
keywords: Cytokine; In vitro; Loading; Model; Osteoarthritis