CD73/5'-ecto-nucleotidase acts as a regulatory factor in osteo-/chondrogenic differentiation of mechanically stimulated mesenchymal stromal cells

• Published in: European cells & materials Vol. 25; pp. 37 - 47
• Main Authors: Ode, A, Schoon, J, Kurtz, A, Gaetjen, M, Ode, J E, Geissler, S, Duda, G N
• Format: Journal Article
• Language: English
• Published: Switzerland Forum Multimedia Publishing LLC 08.01.2013
• Subjects: 5'-Nucleotidase - antagonists & inhibitors; 5'-Nucleotidase - metabolism; Adenosine Diphosphate - analogs & derivatives; Adenosine Diphosphate - pharmacology; Alkaline Phosphatase - metabolism; Animals; Antigens, CD - metabolism; CD73/5’-ecto-nucleotidase; Cell Differentiation; Cell Proliferation; Cells, Cultured; Chondrogenesis; chondrogenic differentiation; Gene Expression; Male; mechanical stimulation; Mesenchymal Stem Cells - enzymology; Mesenchymal Stem Cells - physiology; Mesenchymal stromal cells; Osteoblasts - enzymology; Osteogenesis; osteogenic differentiation; Rats; Rats, Inbred Lew; Receptor, Adenosine A2A - genetics; Receptor, Adenosine A2A - metabolism; Signal Transduction
• ISSN: 1473-2262; 1473-2262
• DOI: 10.22203/ecm.v025a03

Bone regeneration is influenced by mesenchymal stromal cells (MSCs) and mechanical conditions. How healing outcome and mechanical stability are linked on the cellular level, however, remains elusive. Cyclic-compressive loading of MSCs affects the expression of molecules involved in angiogenesis and matrix assembly, but also reduces the expression of CD73, an ecto-5'-nucleotidase, which plays a crucial role in extracellular adenosine generation. Although, for almost 20 years, CD73 has been a major cell surface marker defining MSCs, little is known about its function in these cells. Therefore, the aim of this study was to determine the putative involvement of CD73 in MSC differentiation after cyclic-compressive loading. After cultivation in appropriate differentiation media, chondrogenic differentiation ability was significantly increased in loaded MSCs, hence following current models. Through treatment with the CD73 inhibitor adenosine 5'-(α, β-methylene) diphosphate, chondrogenic matrix deposition was further increased; in contrast, mineral matrix deposition and expression of osteogenic markers was reduced. One major signal transduction pathway, which is activated via CD73-mediated adenosine, is the adenosine receptor pathway. Thus, the adenosine receptor expression pattern was investigated. MSCs expressed the four known adenosine receptors at the mRNA level. After mechanical stimulation of MSCs, Adora2a was down-regulated. These data point towards a role of CD73 in MSC differentiation possibly via A2AR signalling, which is mutually regulated with CD73. In conclusion, the findings of this study suggest that CD73 is another regulatory factor in osteo-/chondrogenic differentiation of MSCs and may provide a - thus far underestimated - therapeutic target to guide bone regeneration.