L C Tetlow1, D E Woolley. 1. University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. lynne.c.tetlow@man.ac.uk
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 1alpha,25 dihydroxyvitaminD(3)(1alpha,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 1alpha25(OH)(2)D(3)on MMP and PGE(2)production by HAC in vitro, with and without stimulation by TNFalpha 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, 1alpha25(OH)(2)D(3)alone had no effect on MMP-1, -9 and PGE(2)production by HAC, but MMP-3 production was up-regulated by 1alpha25(OH)(2)D(3)either with or without stimulation with TNFalpha or PMA. By contrast the increased production of MMP-9 and PGE(2)induced by PMA was significantly suppressed by concomitant treatment with 1alpha25(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 1alpha25(OH)(2)D(3)contributes to the regulation of MMP and PGE(2)production by HAC in osteoarthritic cartilage.
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 1alpha,25 dihydroxyvitaminD(3)(1alpha,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 1alpha25(OH)(2)D(3)on MMP and PGE(2)production by HAC in vitro, with and without stimulation by TNFalpha 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, 1alpha25(OH)(2)D(3)alone had no effect on MMP-1, -9 and PGE(2)production by HAC, but MMP-3 production was up-regulated by 1alpha25(OH)(2)D(3)either with or without stimulation with TNFalpha or PMA. By contrast the increased production of MMP-9 and PGE(2)induced by PMA was significantly suppressed by concomitant treatment with 1alpha25(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 1alpha25(OH)(2)D(3)contributes to the regulation of MMP and PGE(2)production by HAC in osteoarthritic cartilage.
Authors: Rowan T Chlebowski; Karen C Johnson; Dorothy Lane; Mary Pettinger; Charles L Kooperberg; Jean Wactawski-Wende; Tom Rohan; Mary Jo O'Sullivan; Shagufta Yasmeen; Robert A Hiatt; James M Shikany; Mara Vitolins; Janu Khandekar; F Allan Hubbell Journal: Maturitas Date: 2010-11-18 Impact factor: 4.342
Authors: Gabby B Joseph; Charles E McCulloch; Michael C Nevitt; Jan Neumann; John A Lynch; Nancy E Lane; Thomas M Link Journal: Arthritis Care Res (Hoboken) Date: 2020-09 Impact factor: 4.794