Periodontitis Research Today is a free monthly online journal that collates and summarizes the latest research about Periodontitis, including details on treatment, causes, gingivitis, symptoms.

Extracellular ATP and ATPgammaS suppress the proliferation of human periodontal ligament cells by different mechanisms.

Kawase T, Okuda K, Yoshie H

Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstruction, Institute of Medicine and Dentistry, Niigata University, Niigata, Japan. kawase@dent.niigata-u.ac.jp

BACKGROUND: Periodontitis, similar to many other known inflammatory diseases, is thought to increase adenosine triphosphate (ATP) levels in extracellular spaces. Extracellular ATP acts on specific receptors to modulate the proliferation of various cell types. Platelet-rich plasma (PRP) contains high levels of ectonucleotidase activity capable of degrading ATP. The aim of this study was to investigate the effects of ATP on the proliferation of human periodontal ligament (PDL) cells and how these effects are altered by ectonucleotidases. METHODS: PDL cells were derived from healthy young volunteers. ATP content and DNA synthesis were quantified by a bioluminescence and an enzyme-linked immunosorbent assay, respectively. CD39 and p21(WAF1/cip1) expression was analyzed by Western blot. Apoptosis was evaluated by caspase-3/7 activity, terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) activity, annexin-V-binding, and DNA fragmentation. RESULTS: CD39 and ectonucleotidase-like activity were found in PDL cells and serum, respectively. Because less CD39 is expressed in freshly plated cells, both exogenous ATP and ATPgammaS, a slowly hydrolysable analog, inhibited cell proliferation under low serum conditions. ATP upregulated p21(WAF1/cip1), an inhibitor of cell-cycle progression, whereas ATPgammaS induced caspase-dependent apoptosis. Either upregulation of CD39 or added serum rescued cells from the cytostatic actions of exogenous ATP. CONCLUSIONS: In PDL cells expressing low CD39 levels, both ATP and ATPgammaS inhibited proliferation but by different mechanisms. ATP-induced growth arrest suggests that periodontal tissue regeneration is often suppressed at the site of injury. Furthermore, added ectonucleotidases protected PDL cells from ATP's cytostatic actions, suggesting that ectonucleotidase-rich PRP augments the regenerative actions of its constituent growth factors by protecting against exogenous ATP at clinical sites.

Published 2 April 2007 in J Periodontol, 78(4): 748-56.
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