Cyclic hydrostatic pressure and particles increase synthesis of 1,25-dihydroxyvitamin D 3 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 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 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.