[Frontiers in Bioscience S5, 305-324, January 1, 2013]

Calcium signalling in chondrogenesis: implications for cartilage repair

Csaba Matta1, Roza Zakany1

1Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary


1. Abstract
2. Introduction
3. Adult mesenchymal stem cells in cartilage repair
4. Articular cartilage: from structure to function
5. Chondrogenesis is regulated by interplay between numerous intra- and extracellular factors
6. Calcium signalling: a single messenger with diverse functions
7. Ca2+ entry processes in MSCs and in differentiating or mature chondrocytes
7.1. Voltage-operated Ca2+ entry pathways
7.2. Ligand-operated Ca2+ entry pathways
7.2.1. Purinergic signalling pathways
7.2.2. N-methyl-D-aspartate receptor mediated pathways
7.2.3. Transient Receptor Potential (TRP) pathways
7.3. Ca2+ release from internal stores and store-operated Ca2+ entry
8. Ca2+ elimination processes in MSCs, differentiating and mature chondrocytes
9. Temporal characteristics of Ca2+ dependent signals
9.1. Day-by-day variation of cytosolic Ca2+ concentration
9.2. Ca2+ oscillations in mesenchymal stem cells and chondrocytes
10. Ca2+ signalling during mechanotransduction
11. Conclusions
12. Acknowledgements
13. References


Undifferentiated mesenchymal stem cells (MSCs) represent an important source for cell-based tissue regeneration techniques that require differentiation towards specific lineages, including chondrocytes. Chondrogenesis, the process by which committed mesenchymal cells differentiate into chondrocytes, is controlled by complex but not yet completely understood mechanisms that involve many components, including intracellular signalling pathways, as well as plasma membrane receptors and ion channels. Some of these signalling components are Ca2+ sensitive. Although the Ca2+-signalling toolkit of undifferentiated MSCs and mature chondrocytes are extensively studied, the adaptation of these components during differentiation and their role in chondrogenesis is not adequately established. In this review, various aspects of Ca2+ signalling are discussed in MSCs and in mature chondrocytes including spatial and temporal aspects, as well as Ca2+ entry and elimination processes, with implications for their involvement in chondrogenesis. A better understanding of these pathways is envisaged to provide a more efficient differentiation of MSCs towards chondrocytes that may lead to the development of better cartilage tissue engineering techniques.