title: Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game.
abstract: Protein phosphorylation plays a determining role in the regulation of chondrogenesis in vitro. While signalling pathways governed by protein kinases including PKA, PKC, and mitogen-activated protein kinases (MAPK) have been mapped in great details, published data relating to the specific role of phosphoprotein phosphatases (PPs) in differentiating chondroprogenitor cells or in mature chondrocytes is relatively sparse. This review discusses the known functions of Ser/Thr-specific PPs in the molecular signalling pathways of chondrogenesis. PPs are clearly equally important as protein kinases to counterbalance the effect of reversible protein phosphorylation. Of the main Ser/Thr PPs, some of the functions of PP1, PP2A and PP2B have been characterised in the context of chondrogenesis. While PP1 and PP2A appear to negatively regulate chondrogenic differentiation and maintenance of chondrocyte phenotype, calcineurin is an important stimulatory mediator during chondrogenesis but becomes inhibitory in mature chondrocytes. Furthermore, PPs are implicated to be mediators during the pathogenesis of osteoarthritis that makes them potential therapeutic targets to be exploited in the close future. Among the many yet unexplored targets of PPs, modulation of plasma membrane ion channel function and participation in mechanotransduction pathways are emerging novel aspects of signalling during chondrogenesis that should be further elucidated. Besides the regulation of cellular ion homeostasis, other potentially significant novel roles for PPs during the regulation of in vitro chondrogenesis are discussed.
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary; School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Duke of Kent Building, Guildford, Surrey GU2 7XH, United Kingdom. Electronic address: matta.csaba@med.unideb.hu.
authors.forename: Csaba
authors.initials: C
authors.lastname: Matta
authors.affiliation: School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Duke of Kent Building, Guildford, Surrey GU2 7XH, United Kingdom; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom; Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah, 21589, Kingdom of Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Mobasheri
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary.
authors.forename: Róza
authors.initials: R
authors.lastname: Zákány
mesh_terms: D019703:Calcineurin / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D016559:Tacrolimus
keywords: Calcineurin; Calcium signalling; Cartilage; Ion channel; Osteoarthritis; Protein kinase