UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation

Orriss, IR; Arnett, TR; George, J; Witham, MD; (2016) Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation. Experimental Cell Research , 342 (2) pp. 166-174. 10.1016/j.yexcr.2016.03.004. Green open access

[img]
Preview
Text
Arnett_Exp Cell Res 342%2C 166-174 (2016).pdf

Download (3MB) | Preview

Abstract

Allopurinol and its active metabolite, oxypurinol are widely used in the treatment of gout and hyperuricemia. They inhibit xanthine oxidase (XO) an enzyme in the purine degradation pathway that converts xanthine to uric acid. This investigation examined the effect of allopurinol and oxypurinol on bone formation, cell number and viability, gene expression and enzyme activity in differentiating and mature, bone-forming osteoblasts. Although mRNA expression remained relatively constant, XO activity decreased over time with mature osteoblasts displaying reduced levels of uric acid (20% decrease). Treatment with allopurinol and oxypurinol (0.1-1µM) reduced XO activity by up to 30%. At these concentrations, allopurinol and oxypurinol increased bone formation by osteoblasts ~4-fold and ~3-fold, respectively. Cell number and viability were unaffected. Both drugs increased tissue non-specific alkaline phosphatase (TNAP) activity up to 65%. Osteocalcin and TNAP mRNA expression was increased, 5-fold and 2-fold, respectively. Expression of NPP1, the enzyme responsible for generating the mineralisation inhibitor, pyrophosphate, was decreased 5-fold. Col1α1 mRNA expression and soluble collagen levels were unchanged. Osteoclast formation and resorptive activity were not affected by treatment with allopurinol or oxypurinol. Our data suggest that inhibition of XO activity promotes osteoblast differentiation, leading to increased bone formation in vitro.

Type: Article
Title: Allopurinol and oxypurinol promote osteoblast differentiation and increase bone formation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.yexcr.2016.03.004
Publisher version: http://dx.doi.org/10.1016/j.yexcr.2016.03.004
Language: English
Additional information: Copyright © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Allopurinol, Bone formation, Osteoblast differentiation, Oxypurinol
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1477592
Downloads since deposit
58Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item