Cyclic hydrostatic pressure and particles increase synthesis of 1,25-dihydroxyvitamin D3 by human macrophages in vitro.

Abstract

1,25-Dihydroxyvitamin D(3) has a pivotal role in bone resorption and osteoclast activity. As activated macrophages are known to synthesise 1,25-dihydroxyvitamin D(3), this study examined whether pressure modulated its synthesis. Pressure and particles have been shown to increase synthesis of pro-resorptive cytokines and other factors by cultured macrophages. Human peripheral blood macrophages were isolated, cultured and exposed to pressure (similar to that found in the human joint) and/or particles. Synthesis of 1,25-dihydroxyvitamin D(3) by macrophages was assayed using high pressure liquid chromatography and in situ hybridization. Synthesis of 1,25-dihydroxyvitamin D(3) but not 24,25-dihydroxyvitamin D(3) was increased in macrophages under pressure. In situ hybridization demonstrated an increase in 1alpha-hydroxylase expression in response to pressure or particles and simultaneous exposure to both stimuli generated higher expression of 1alpha-hydroxylase. In conclusion, this is the first study to demonstrate that mechanical loading, in the form of pressure, stimulates 1,25-dihydroxyvitamin D(3) synthesis in human macrophages. These findings have implications for the in vivo situation, as they suggest that 1,25-dihydroxyvitamin D(3) could be one factor stimulating osteoclastic bone resorption in pathologies, such as arthritis or implant loosening, where intra-articular or intra-osseous pressure is raised or where wear particles interact with macrophages.

• Authors: C E Evans, S Mylchreest, A P Mee, J L Berry, J G Andrew
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 38 Issue 9 Pg. 1540-6 ( 2006) ISSN: 1357-2725 [Print] Netherlands
• PMID: 16690344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Polyethylenes
• ultra-high molecular weight polyethylene
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
• Calcitriol

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (biosynthesis)
• Calcitriol (biosynthesis)
• Cells, Cultured
• Humans
• Hydrostatic Pressure
• In Situ Hybridization
• Macrophages (metabolism)
• Polyethylenes (pharmacology)