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dc.contributor.authorHansen, Ann Kristin
dc.contributor.authorFigenschau, Yngve Anton
dc.contributor.authorMartinez, Inigo Zubiavrre
dc.date.accessioned2018-02-14T14:20:42Z
dc.date.available2018-02-14T14:20:42Z
dc.date.issued2017-11-06
dc.description.abstractBackground: <br> The aim was to investigate whether resident chondrocytes in human articular cartilage and in subculture express vitamin D receptor (VDR) and the enzyme that hydroxylates the prohormone 25(OH)D3 to the active hormone 1α,25(OH)2D3, namely 1α-hydroxylase (CYP27B1). Any putative effects of vitamin D on chondrocytes were also explored. <br> Methods: <br> Cartilage from human osteoarthritic knee joints, cultured chondrocytes and cells grown in 3D spheroids were examined for the expression of VDR and 1α-hydroxylase by PCR, Western blots and immunolabelling. Receptor engagement was judged by visualizing nuclear translocation. The effects of 25(OH)D3 and 1α,25(OH)2D3 on chondrocyte functions were assessed in proliferation-, chondrogenesis- and cartilage signature-gene expression assays. The capability of chondrocytes to hydroxylate 25(OH)D3 was determined by measuring the concentration of metabolites. Finally, a putative regulation of receptor and enzyme expression by 1α,25(OH)2D3 or interleukin (IL)-1β, was investigated by Western blot. <br> Results: <br> Gene expression was positive for VDR in freshly isolated cells from native cartilage, cells subcultured in monolayers and in spheroids, whereas protein expression, otherwise judged low, was apparent in monolayers. Nuclear translocation of VDR occurred upon 1α,25(OH)2D3 treatment. Transcripts for 1α-hydroxylase were detected in freshly isolated cells, cultured cells and spheroids. Western blots and immunolabelling detected 1α-hydroxylase protein in all materials, while staining of tissue appeared confined to cells at the superficial layer. A dose-dependent 1α,25(OH)2D3 production was measured when the enzyme substrate was supplied to cell cultures. Western blots revealed that the VDR, but not 1α-hydroxylase, was induced by IL-1β treatment in adherent cells. Proliferation in monolayers was enhanced by both 25(OH)D3 and 1α,25(OH) 2D3, and both compounds had negative effects on chondrogenesis and cartilage-matrix genes. <br> Conclusions: <br> VDR expression in resident cartilage chondrocytes, generally considered differentiated cells, is elusive. A similar pattern applies for redifferentiated chondrocytes in spheroid cultures, whereas dedifferentiated cells, established in monolayers, stably express VDR. Both 25(OH)D3 and 1α,25(OH)2D3 are able to potentiate cell proliferation but have a negative impact in proteoglycan synthesis. Chondrocytes express 1α-hydroxylase and may contribute to the production of 1α,25(OH)2D3 into the joint environment. Effects of vitamin D could be unfavourable in the context of cartilage matrix synthesis.en_US
dc.descriptionSource at: <a href=https://doi.org/10.1186/s12891-017-1791-y> https://doi.org/10.1186/s12891-017-1791-y </a>en_US
dc.identifier.citationHansen, A. K., Figenschau, Y. & Martinez, I. Z. (2017). Co-expression of 1α-hydroxylase and vitamin D receptor in human articular chondrocytes. BMC Musculoskeletal Disorders, 18(432), 1-13. https://doi.org/10.1186/s12891-017-1791-yen_US
dc.identifier.cristinIDFRIDAID 1513660
dc.identifier.doi10.1186/s12891-017-1791-y
dc.identifier.issn1471-2474
dc.identifier.urihttps://hdl.handle.net/10037/12175
dc.language.isoengen_US
dc.publisherBioMed Centralen_US
dc.relation.journalBMC Musculoskeletal Disorders
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.titleCo-expression of 1α-hydroxylase and vitamin D receptor in human articular chondrocytesen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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