The transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models.

Candida Deves, Thiago Milech de Assunção, Rodrigo Gay Ducati, Maria Martha Campos, Luiz Augusto Basso, Diogenes Santiago Santos, Eraldo L Batista

Graduate Program in Cellular and Molecular Biology, Centro de Pesquisas/ Biologia Molecular e Funcional (CP-BMF), Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS, RS, Brazil.

Bone 2013 Jan

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Purine nucleoside phosphorylase (PNP) is a purine-metabolizing enzyme that catalyzes the reversible phosphorolysis of 6-oxypurine (deoxy)nucleosides to their respective bases and (deoxy)ribose-1-phosphate. It is a key enzyme in the purine salvage pathway of mammalian cells. The present investigation sought to determine whether the PNP transition state analog inhibitor (Immucillin-H) arrests bone loss in two models of induced periodontal disease in rats. Periodontal disease was induced in rats using ligature or LPS injection followed by administration of Immucillin-H for direct analysis of bone loss, histology and TRAP staining. In vitro osteoclast differentiation and activation of T CD4+ cell s in the presence of Immucillin-H were carried out for assessment of RANKL expression, PNP and Cathepsin K activity. Immucillin-H inhibited bone loss induced by ligatures and LPS, leading to a reduced number of infiltrating osteoclasts and inflammatory cells. In vitro assays revealed that Immucillin-H could not directly abrogate differentiation of osteoclast precursor cell s, but affected lymphocyte-mediated osteoclastogenesis. On the other hand, incubation of pre-activated T CD4+ with Immucillin-H decreased RANKL secretion with no compromise of cell viability. The PNP transition state analog Immucillin-H arrests bone loss mediated by T CD4+ cell s with no direct effect on osteoclasts. PNP inhibitor may have an impact in the treatment of diseases characterized by the presence of pathogens and imbalances of bone metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Candida Deves, Thiago Milech de Assunção, Rodrigo Gay Ducati, Maria Martha Campos, Luiz Augusto Basso, Diogenes Santiago Santos, Eraldo L Batista. The transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models. Bone. 2013 Jan;52(1):167-75