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Type: Journal article
Title: Vitamin D receptor expression in mature osteoclasts reduces bone loss due to low dietary calcium intake in male mice
Author: Starczak, Y.
Reinke, D.C.
Barratt, K.R.
Russell, P.K.
Clarke, M.V.
Davey, R.A.
Atkins, G.J.
Anderson, P.H.
Citation: The Journal of Steroid Biochemistry and Molecular Biology, 2021; 210:1-7
Publisher: Elsevier
Issue Date: 2021
ISSN: 0960-0760
Statement of
Yolandi Starczak, Daniel C. Reinke, Kate R. Barratt, Patricia K. Russell, Michelle V. Clarke, Rachel A. Davey, Gerald J. Atkins, Paul H. Anderson
Abstract: Mature osteoclasts express the vitamin D receptor (VDR) and are able to respond to active vitamin D (1α, 25-dihydroxyvitamin D3; 1,25(OH)2D3) by regulating cell maturation and activity. However, the in vivo consequences of vitamin D signalling directly within functionally mature osteoclasts is only partially understood. To investigate the in vivo role of VDR in mature osteoclasts, conditional deletion of the VDR under control of the cathepsin K promoter (CtskCre/Vdr−/−), was assessed in 6 and 12-week-old mice, either under normal dietary conditions (NormCaP) or when fed a low calcium (0.03 %), low phosphorous (0.08 %) diet (LowCaP). Splenocytes from CtskCre/Vdr−/− mice were co-cultured with MLO-Y4 osteocyte-like cells to assess the effect on osteoclastogenesis. Six-week-old CtskCre/Vdr-/- mice demonstrated a 10 % decrease in vertebral bone volume (p < 0.05), which was associated with increased osteoclast size (p < 0.05) when compared to Vdrfl/fl control mice. Control mice fed a LowCaP diet exhibited extensive trabecular bone loss associated with increased osteoclast surface, number and size (p < 0.0001). Interestingly, CtskCre/Vdr-/- mice fed a LowCaP diet showed exacerbated loss of bone volume fraction (BV/TV%) and trabecular number (Tb.N), by a further 22 % and 21 %, respectively (p < 0.05), suggesting increased osteoclastic bone resorption activity with the loss of VDR in mature osteoclasts under these conditions. Co-culture of CtskCre/Vdr-/- splenocytes with MLO-Y4 cells increased resulting osteoclast numbers 2.5-fold, which were greater in nuclei density and exhibited increased resorption of dentine compared to osteoclasts derived from Vdrfl/fl splenocyte cultures. These data suggest that in addition to RANKL-mediated osteoclastogenesis, intact VDR signalling is required for the direct regulation of the differentiation and activity of osteoclasts in both in vivo and ex vivo settings.
Keywords: Vitamin D receptor; 1α,25-dihydroxyvitamin D₃; Osteoclasts; Osteoclastogenesis; Bone resorption
Description: Available online 26 February 2021
Rights: © 2021 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.jsbmb.2021.105857
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