Original Full Length ArticleThe transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models

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.

► The effect of a PNP inhibitor was evaluated in rat models of periodontal disease and cellular assays. ► The pharmacological inhibition PNP activity blocks periodontal bone loss induced by ligatures or LPS in rats. ► Bone loss arrest was mediated by regulation of T CD4 + cells. ► No direct effects on osteoclast activity and osteoclastogenesis was evidenced by the pharmacological inhibition of PNP. ► PNP transition state analogs deserve attention as potential drugs in the treatment of diseases that involve bone resorption.