Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic cartilage and human articular chondrocytes in vitro

AbstractObjectives To examine the in situ distributions of vitamin D receptors (VDR) and matrix metalloproteinases (MMPs) in osteoarthritic cartilage for comparison with non-arthritic, normal cartilage; and to assess the in vitro effects of 1α,25 dihydroxyvitaminD3(1α,25(OH)2D3) on MMPs-1, -3 and -9 and prostaglandin E2(PGE2) production by cultures of human articular chondrocytes (HAC) shown to be VDR-positive.Methods Using immunohistochemistry VDR expression in different specimens of osteoarthritic cartilage (N=11) was compared to that in normal cartilage (N=6), along with the immunodetection of MMPs-1, -3 and -9. The effects of 1α25(OH)2D3on MMP and PGE2production by HAC in vitro, with and without stimulation by TNFα or phorbol myristate acetate (PMA), was evaluated using ELISA methodology.Results VDR was demonstrated in HAC of all specimens of osteoarthritic cartilage, especially the superficial zone, whereas only two of five normal cartilage specimens were VDR+for a minor proportion of HAC. Immunolocalization of MMPs-1, -3 and -9 was often seen in areas where chondrocytes were VDR+, and dual immunolocalization has demonstrated individual chondrocytes positive for both VDR and MMP-3 in situ. In vitro, 1α25(OH)2D3alone had no effect on MMP-1, -9 and PGE2production by HAC, but MMP-3 production was up-regulated by 1α25(OH)2D3either with or without stimulation with TNFα or PMA. By contrast the increased production of MMP-9 and PGE2induced by PMA was significantly suppressed by concomitant treatment with 1α25(OH)2D3.Conclusions The demonstration of VDR expression by HAC in osteoarthritic cartilage was often associated with sites where MMP expression was prevalent, observations in contrast to their virtual absence in normal age-matched cartilage. Together with HAC in vitro studies, the data suggests that 1α25(OH)2D3contributes to the regulation of MMP and PGE2production by HAC in osteoarthritic cartilage