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

Autor: D.E. Woolley, L.C. Tetlow
Rok vydání: 2001
Předmět:
Cartilage
Articular
medicine.medical_specialty
Calcitriol
medicine.medical_treatment
Biomedical Engineering
Cartilage metabolism
Osteoarthritis
Matrix metalloproteinase
Calcitriol receptor
Dinoprostone
Chondrocytes
Rheumatology
Internal medicine
Osteoarthritis
Vitamin D receptors
1α
25dihydroxyvitaminD3
Matrix metalloproteinases
Chondrocytes
Prostaglandin E2
medicine
Humans
Orthopedics and Sports Medicine
Receptor
Cells
Cultured
Aged
Tumor Necrosis Factor-alpha
Chemistry
Cartilage
Middle Aged
Osteoarthritis
Knee
medicine.disease
Immunohistochemistry
Matrix Metalloproteinases
Stimulation
Chemical
Calcium Channel Agonists
medicine.anatomical_structure
Endocrinology
Matrix Metalloproteinase 9
Receptors
Calcitriol
Tetradecanoylphorbol Acetate
Matrix Metalloproteinase 3
lipids (amino acids
peptides
and proteins)
medicine.drug
Prostaglandin E
Zdroj: Osteoarthritis and Cartilage. 9:423-431
ISSN: 1063-4584
DOI: 10.1053/joca.2000.0408
Popis: 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 1α,25 dihydroxyvitaminD 3 (1α,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 1α25(OH) 2 D 3 on MMP and PGE 2 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 , 1α25(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 1α25(OH) 2 D 3 either with or without stimulation with TNFα or PMA. By contrast the increased production of MMP-9 and PGE 2 induced by PMA was significantly suppressed by concomitant treatment with 1α25(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 1α25(OH) 2 D 3 contributes to the regulation of MMP and PGE 2 production by HAC in osteoarthritic cartilage.
Databáze: OpenAIRE
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