Xanthine Oxidase Mediates Cytokine-induced, but not Hormone-induced Bone Resorption

• Published in: Free radical research 2003-01, Vol.37 (2), p.179-187
• Main Authors: Kanczler, Janos M., Millar, Timothy M., Bodamyali, Tulin, Blake, David R., Stevens, Cliff R.
• Format: Article
• Language: English
• Subjects: Allopurinol - pharmacology; Animals; Animals, Newborn; Bone and Bones - metabolism; Bone Resorption; Catalase - pharmacology; Cells, Cultured; Cholecalciferol - metabolism; Cytokines; Cytokines - metabolism; Dose-Response Relationship, Drug; Hormones - metabolism; Hydrogen Peroxide; Hydrogen Peroxide - pharmacology; Interleukin-1 - metabolism; Male; Mice; Oxidation-Reduction; Parathyroid Hormone - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species; Tumor Necrosis Factor-alpha - metabolism; Xanthine Oxidase; Xanthine Oxidase - pharmacology
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/1071576021000040673

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) have been implicated as mediators of osteoclastic bone resorption. Xanthine oxidase (XO) a ubiquitous enzyme is widely known for its production of these ROS. We therefore evaluated the potential of XO as a source of ROS in cytokine- and hormone-induced bone resorption. XO activity in rat calvarial osteoblasts was found to be significantly elevated upon stimulation by the cytokines, TNF &#102 and IL-1 &#103 . These cytokines also caused a dose related increase in bone resorption of mouse calvariae, which was significantly inhibited by catalase (10 IU/ml). Allopurinol, the competitive inhibitor of XO, also caused a dose related (1-50 &#119 M) inhibition of TNF &#102 (20 ng/ml) and (0.01-10 &#119 M) IL-1 &#103 (50 IU/ml)-induced bone resorption, respectively. PTH- and 1,25-(OH)2 Vitamin D3-induced bone resorption could also be inhibited by catalase (100 IU/ml) but was unaffected by allopurinol, indicating that another mediator, other than XO, is required for hormone-induced bone resorption. These results demonstrate, that modulation of the redox balance in the bone microenvironment, which contains XO, can affect the bone resorbing process. Therefore, XO may play a pivotal role in cytokine-induced bone resorption and, if manipulated appropriately, could show a therapeutic benefit in inflammatory bone disorders such as RA.