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

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 alpha ,25 dihydroxyvitaminD(3) (1 alpha ,25(OH)(2)D(3)) on MMPs-1, -3 and -9 and prostaglandin E(2) (PGE(2)) 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 alpha 25(OH)(2)D(3). on MMP and PGE(2) production by HAC in vitro, with and without stimulation by TNF alpha 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 alpha 25(OH)(2)D(3) alone had no effect on MMP-1, -9 and PGE2 production by HAC, but MMP-3 production was up-regulated by 1 alpha 25(OH)(2)D(3) either with or without stimulation with TNF alpha or PMA. By contrast the increased production of MMP-9 and PGE(2) induced by PMA was significantly suppressed by concomitant treatment with 1 alpha 25(OH)(2)D(3). 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 alpha 25(OH)(2)D(3) contributes to the regulation of MMP and PGE(2) production by HAC in osteoarthritic cartilage. (C) 2001 OsteoArthritls Research Society International.