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This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 102/3/1152    most recent 00535.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Qi, J. Articles by Banes, A. J. Search for Related Content PubMed PubMed Citation Articles by Qi, J. Articles by Banes, A. J.

ATP reduces gel compaction in osteoblast-populated collagen gels

¹Flexcell International Corporation, Hillsborough; ²Joint Department of Biomedical Engineering of North Carolina at Chapel Hill and North Carolina State University, Raleigh; and Departments of ³Cell and Molecular Physiology, ⁴Genetics, and ⁵Curriculum in Applied and Materials Science, University of North Carolina, Chapel Hill, North Carolina

Submitted 12 May 2006 ; accepted in final form 21 November 2006

Bone remodeling is a localized process, but regulated by systemic signals such as hormones, cytokines, and mechanical loading. The mechanism by which bone cells convert these systemic signals into local signals is not completely understood. It is broadly accepted that the "prestress" in cytoskeleton of cells affects the magnitude of cellular responses to mechanical stimuli. Prestress derives from stiff cytoskeletal proteins and their connections within the cell and from cell contractility upon attaching to matrix. In an in vitro model of three-dimensional gel compaction, the relative cellular prestress levels in the same matrix environment were determined by matrix compaction rate: a greater compaction rate resulted in a higher level of prestress. In the present study, the effects of ATP on the prestress of osteoblasts were studied using mouse MC3T3-E1 cells grown in three-dimensional bioartificial tissues (BATs). ATP (100 µM) reduced the compaction rate of BATs in a dose-dependent manner. ADP, 2'-(or 3')-O-(4-benzoylbenzoyl) ATP, and UTP, but not ,-methylene ATP, also reduced the compaction rate but to a lesser extent. Pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium did not block the effect of ATP on BAT compaction rate. These results indicate that both P2X and P2Y receptors are involved in ATP-induced reduction of BAT compaction rate. Steady fluid flow and RT-PCR results showed that ATP reduced cell attachment on type I collagen by downregulating the expression of integrin ₁. These results suggest a potential role for P2 receptors in matrix remodeling and repair and as a potential drug target in treatment of bone diseases.

adenosine triphosphate; three-dimensional culture; purinoceptor; osteoblast; extracellular matrix