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

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...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1473-2262 1473-2262
DOI:	10.22203/ecm.v025a03