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

Abstract

Objectives: 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 1 α,25 dihydroxyvitaminD3 (1 α,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 1 α25(OH)2D3 on MMP and PGE2 production 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, 1 α25(OH)2D3 alone had no effect on MMP-1, -9 and PGE2 production by HAC, but MMP-3 production was up-regulated by 1 α25(OH)2D3 either with or without stimulation with TNFα or PMA. By contrast the increased production of MMP-9 and PGE2 induced by PMA was significantly suppressed by concomitant treatment with 1 α25(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 1 α25(OH)2D3 contributes to the regulation of MMP and PGE2 production by HAC in osteoarthritic cartilage. © 2001 OsteoArthritis Research Society International.