Both ligand and VDR expression levels critically determine the effect of 1α,25-dihydroxyvitamin-D3 on osteoblast differentiation

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dc.contributor.author Yang, Dongqing
dc.contributor.author Anderson, Paul H.
dc.contributor.author Wijeyanaka, Asiri R.
dc.contributor.author Barratt, Kate R.
dc.contributor.author Triliana, Rahma
dc.contributor.author Stapledon, Catherine J.M.
dc.contributor.author Zhou, Hong
dc.contributor.author Findlay, David M.
dc.contributor.author Morris, Howard A.
dc.contributor.author Atkins, Gerald J.
dc.date.accessioned 2022-02-23T05:13:39Z
dc.date.available 2022-02-23T05:13:39Z
dc.date.issued 2018
dc.identifier.uri https://www.sciencedirect.com/science/article/abs/pii/S0960076017302510
dc.identifier.uri http://repository.unisma.ac.id/handle/123456789/3111
dc.description [ARCHIVES] Copyright Article from: The Journal of Steroid Biochemistry and Molecular Biology en_US
dc.description.abstract Previous studies have shown that 1α,25-dihydroxyvitamin D3 (1,25D) through vitamin D receptor (VDR) signalling has both catabolic and anabolic effects on osteoblast differentiation. However, the mechanism of these differential effects by 1,25D is not fully understood. In this study, mice with three different genetic backgrounds, representing a normal VDR level (wild-type, WT), VDR over-expression specifically in mature osteoblasts (ObVDR-B6) and global VDR knockout (VDRKO), were utilised to generate primary osteoblast-like cultures to further elucidate the effects of 1,25D on osteoblast differentiation. Our data confirm the importance of VDR in the late stage of osteogenic differentiation and also for the expression of factors critical for osteoblastic support of osteoclast formation. This study also demonstrates the differential effects of a pharmacological level of 1,25D (1 nM) on the expression of osteogenic differentiation markers, including Ocn and Sost, depending on the relative level of VDR. Our findings suggest that 1,25D plays an inhibitory role in matrix mineralisation, possibly through the modulation of the tissue non-specific alkaline phosphatase to ectonucleotide pyrophosphatase/phosphodiesterase 1 axis, in a VDR level-dependent manner. We conclude that the relative VDR level and the 1,25D availability to cells, are important co-determinants for whether 1,25D plays a promoting or suppressive role in osteoblast-mediated osteogenic activity. en_US
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries The Journal of Steroid Biochemistry and Molecular Biology;Vol.177, Page 83-90
dc.subject Vitamin D en_US
dc.subject Osteoblast en_US
dc.subject VDR en_US
dc.subject Mineralisation en_US
dc.subject VDR knockout en_US
dc.subject Differentiation en_US
dc.title Both ligand and VDR expression levels critically determine the effect of 1α,25-dihydroxyvitamin-D3 on osteoblast differentiation en_US
dc.type Article en_US


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