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

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2 Scopus citations

Abstract

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. + cells 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 cells, 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. + cells 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.

Original languageEnglish (US)
Pages (from-to)167-175
Number of pages9
JournalBone
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

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Keywords

  • Animal models
  • Bone loss
  • Osteoclasts
  • Periodontal disease
  • Purine nucleoside phophorylase
  • T-lymphocyte

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Deves, C., de Assunção, T. M., Ducati, R. G., Campos, M. M., Basso, L. A., Santos, D. S., & Batista, E. L. (2013). The transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models. Bone, 52(1), 167-175. https://doi.org/10.1016/j.bone.2012.09.026