Xanthine oxidase mediates cytokine-induced, but not hormone-induced bone resorption

J M Kanczler, T M Millar, T Bodamyali, D R Blake, C R Stevens

Research output: Contribution to journalArticle

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Abstract

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, TNFalpha and IL-1beta. 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 muM) inhibition of TNFalpha (20 ng/ml) and (0.01-10 muM) IL-1beta (50 IU/ml)-induced bone resorption, respectively. PTH- and 1,25-(OH)(2) Vitamin D-3-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.
Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalFree Radical Research
Volume37
Issue number2
DOIs
Publication statusPublished - 2003

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Xanthine Oxidase
Bone Resorption
Bone
Hormones
Cytokines
Reactive Oxygen Species
Allopurinol
Bone and Bones
Catalase
Tumor Necrosis Factor-alpha
Cholecalciferol
Osteoblasts
Skull
Interleukin-10
Hydrogen Peroxide
Oxidation-Reduction
Rats
Enzymes
Modulation

Cite this

Kanczler, J. M., Millar, T. M., Bodamyali, T., Blake, D. R., & Stevens, C. R. (2003). Xanthine oxidase mediates cytokine-induced, but not hormone-induced bone resorption. Free Radical Research, 37(2), 179-187. https://doi.org/10.1080/1071576021000040673

Xanthine oxidase mediates cytokine-induced, but not hormone-induced bone resorption. / Kanczler, J M; Millar, T M; Bodamyali, T; Blake, D R; Stevens, C R.

In: Free Radical Research, Vol. 37, No. 2, 2003, p. 179-187.

Research output: Contribution to journalArticle

Kanczler, JM, Millar, TM, Bodamyali, T, Blake, DR & Stevens, CR 2003, 'Xanthine oxidase mediates cytokine-induced, but not hormone-induced bone resorption', Free Radical Research, vol. 37, no. 2, pp. 179-187. https://doi.org/10.1080/1071576021000040673
Kanczler, J M ; Millar, T M ; Bodamyali, T ; Blake, D R ; Stevens, C R. / Xanthine oxidase mediates cytokine-induced, but not hormone-induced bone resorption. In: Free Radical Research. 2003 ; Vol. 37, No. 2. pp. 179-187.
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