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TISSUE-SPECIFIC STEM CELLS

Polyamines Modulate Nitric Oxide Production and Cox-2 Gene Expression in Response to Mechanical Loading in Human Adipose Tissue-Derived Mesenchymal Stem Cells

^aDepartment of Oral Cell Biology, Academic Center of Dentistry Amsterdam, Universiteit van Amsterdam, and Vrije Universiteit, and
^bDepartment of Orthopaedic Surgery, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands

Key Words. Polyamines • Adipose tissue-derived mesenchymal stem cells • Mechanical loading • Fluid shear stress • Fluid flow • Nitric oxide • Spermidine/spermine N (1)-acetyltransferase • Cyclooxygenase-2 • Bone cells

Jenneke Klein-Nulend, Ph.D., ACTA-Vrije Universiteit, Department of Oral Cell Biology, Van der Boechorststraat 7, NL-1081 BT Amsterdam, The Netherlands. Telephone: +31-20 444 8660; Fax: +31-20 444 8683; e-mail: j.kleinnulend{at}vumc.nl

Received December 13, 2005; accepted for publication June 15, 2006.
First published online in STEM CELLS EXPRESS   June 22, 2006.



For bone tissue engineering, it is important that mesenchymal stem cells (MSCs) display a bone cell-like response to mechanical loading. We have shown earlier that this response includes increased nitric oxide (NO) production and cyclooxygenase-2 (COX-2) gene expression, both of which are intimately involved in mechanical adaptation of bone. COX-2 gene expression is likely regulated by polyamines, which are organic cations implicated in cell proliferation and differentiation. This has led to the hypothesis that polyamines may play a role in the response of adipose tissue-derived MSCs (AT-MSCs) to mechanical loading. The aim of this study was to investigate whether genes involved in polyamine metabolism are regulated by mechanical loading and to study whether polyamines modulate mechanical loading-induced NO production and COX-2 gene expression in human AT-MSCs. Human AT-MSCs displayed a bone cell-like response to mechanical loading applied by pulsating fluid flow (PFF), as demonstrated by increased NO production and increased gene expression of COX-2. Furthermore, PFF increased gene expression of spermidine/spermine N (1)-acetyltransferase, which is involved in polyamine catabolism, suggesting that mechanical loading modulates polyamine levels. Finally, the polyamine spermine was shown to inhibit both PFF-induced NO production and COX-2 gene expression, suggesting that polyamines modulate the response of human AT-MSCs to mechanical loading. In conclusion, this is the first study implicating polyamines in the response of human AT-MSCs to mechanical loading, creating opportunities for the use of polyamines in tissue engineering approaches targeting skeletal defects.

This article has been cited by other articles:

				A. Schaffler and C. Buchler Concise Review: Adipose Tissue-Derived Stromal Cells--Basic and Clinical Implications for Novel Cell-Based Therapies Stem Cells, April 1, 2007; 25(4): 818 - 827. [Abstract] [Full Text] [PDF]