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Cell Signal. 2014 Oct;26(10):2175-85. doi: 10.1016/j.cellsig.2014.06.013. Epub 2014 Jul 4.

Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game.

Author information

  • 1Department 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.
  • 2School 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.
  • 3Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary.
  • 4Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032, Debrecen, Hungary.

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Calcineurin; Calcium signalling; Cartilage; Ion channel; Osteoarthritis; Protein kinase

PMID:
25007994
[PubMed - in process]
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