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

C. E. Evans, S. Mylchreest, A. P. Mee, J. L. Berry, J. G. Andrew

Research output: Contribution to journalArticlepeer-review


1,25-Dihydroxyvitamin D3 has a pivotal role in bone resorption and osteoclast activity. As activated macrophages are known to synthesise 1,25-dihydroxyvitamin D3, 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 D3 by macrophages was assayed using high pressure liquid chromatography and in situ hybridization. Synthesis of 1,25-dihydroxyvitamin D3 but not 24,25-dihydroxyvitamin D3 was increased in macrophages under pressure. In situ hybridization demonstrated an increase in 1α-hydroxylase expression in response to pressure or particles and simultaneous exposure to both stimuli generated higher expression of 1α-hydroxylase. In conclusion, this is the first study to demonstrate that mechanical loading, in the form of pressure, stimulates 1,25-dihydroxyvitamin D3 synthesis in human macrophages. These findings have implications for the in vivo situation, as they suggest that 1,25-dihydroxyvitamin D3 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. © 2006 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1540-1546
Number of pages6
JournalInternational Journal of Biochemistry and Cell Biology
Issue number9
Publication statusPublished - 2006


  • 1,25-Dihydroxyvitamin D3
  • Bone pathologies
  • Hydrostatic pressure
  • Macrophages
  • Ultra-high molecular weight polyethylene particles


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