ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells.

ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Research Abstract Details 

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ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Abstract Text:

Ryan C Riddle,Amanda F Taylor,Jennifer R Rogers,Henry J Donahue,

Oscillatory fluid flow induced the vesicular release of ATP from human BMSCs that directly contributes to the induction of BMSC proliferation. Degrading extracellular nucleotides prevents fluid flow-induced increases in intracellular calcium concentration, the activation of calcineurin, and the nuclear translocation of NFAT. INTRODUCTION: Regulation of bone cell activity by autocrine/paracrine factors is a well-established mechanism by which skeletal homeostasis is regulated by mechanical signals. The release of extracellular nucleotides in particular has been shown to induce many of the responses thought to be necessary for load-induced bone formation. In these studies, we examined the effect of oscillatory fluid flow on the release of ATP from bone marrow stromal cells (BMSCs) and the effect of ATP release on BMSC proliferation and intracellular calcium signaling pathways. MATERIALS AND METHODS: BMSCs were exposed to oscillatory fluid flow, and the concentration of ATP in conditioned media samples was determined using a luciferin:luciferase-based reaction. Western blot analysis was used to examine the expression of purinergic receptors. Using pharmacological antagonists of gap junction hemichannels and vesicular trafficking, we studied the mechanism of ATP release from BMSCs. Apyrase was used to study the effect of extracellular nucleotides on intracellular calcium concentration, calcineurin activity, and nuclear factor of activated T cells (NFAT) nuclear translocation. RESULTS AND CONCLUSIONS: Fluid flow exposure induced the flow rate-dependent release of ATP from BMSCs that was attenuated by treatment with monensin and N-ethylmaleimide, suggesting a vesicular mechanism. Treating BMSCs with ATP, but not other nucleotides, increased cellular proliferation. Moreover, extracellular ATP was a prerequisite for fluid flow-induced increases in intracellular calcium concentration, activation of calcineurin, the nuclear translocation of NFATc1, and proliferation. These data indicate that ATP regulates not only osteoblastic and osteocytic cell behavior but also that of mesenchymal precursors and support our hypothesis that similar mechanotransduction mechanisms are activated by fluid flow in these cell types.

ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Publishing Authors By Initials

RC Riddle,AF Taylor,JR Rogers,HJ Donahue,

For similar cells: connective tissue cells: stromal cells research abstracts see: cells: connective tissue cells: stromal cells research

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MEDLINE DATE:

ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of bone and mineral research : the officia

VOLUME: 22

Page Numbers: 589-600

Journal Abbreviation: J. Bone Miner. Res.

ISSN: 0884-0431

DAY: 3

MONTH: Apr

YEAR: 2007

ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8610640

ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Keywords Mesh Terms:

KEYWORDS: Stromal Cells

MESH TERMS: metabolism

Chemical & Substance for Abstract: ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells. Information

Substance Name: Adenosine Triphosphate

Registry Number: 56-65-5

Grant and Affiliation Information for ATP release mediates fluid flow-induced proliferation of human bone marrow stromal cells.

AFFILIATION: Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, Pennsylvania State University College of Medicine, Milton S Hershey Medical Center, Hershey, PA 17033, USA.

Country: United States

AGENCY: United States NIA

GRANT: AG13087

ACRONYM: AG

MEDLINETA: J Bone Miner Res

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