title: 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.affiliation: Division of Laboratory & Regenerative Medicine, Stopford Building, The Medical School, University of Manchester, Oxford Road, Manchester M13 9PT, UK. c.e.evans@manchester.ac.uk
authors.forename: C E
authors.initials: CE
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Mylchreest
authors.forename: A P
authors.initials: AP
authors.lastname: Mee
authors.forename: J L
authors.initials: JL
authors.lastname: Berry
authors.forename: J G
authors.initials: JG
authors.lastname: Andrew
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D002117:Calcitriol / Q000096:biosynthesis*; D002478:Cells, Cultured; D006801:Humans; D006874:Hydrostatic Pressure; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism*; D011095:Polyethylenes / Q000494:pharmacology*
chemical_list: D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol