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The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling

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The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling. / Kaiser, Martin F; Heider, Ulrike; Mieth, Maren; Zang, Chuanbing; von Metzler, Ivana; Sezer, Orhan.

In: EUR J HAEMATOL, Vol. 90, No. 4, 01.04.2013, p. 263-72.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kaiser, MF, Heider, U, Mieth, M, Zang, C, von Metzler, I & Sezer, O 2013, 'The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling', EUR J HAEMATOL, vol. 90, no. 4, pp. 263-72. https://doi.org/10.1111/ejh.12069

APA

Kaiser, M. F., Heider, U., Mieth, M., Zang, C., von Metzler, I., & Sezer, O. (2013). The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling. EUR J HAEMATOL, 90(4), 263-72. https://doi.org/10.1111/ejh.12069

Vancouver

Kaiser MF, Heider U, Mieth M, Zang C, von Metzler I, Sezer O. The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling. EUR J HAEMATOL. 2013 Apr 1;90(4):263-72. https://doi.org/10.1111/ejh.12069

Bibtex

@article{51457a47e2fa48eb9093bc10c0766dfa,
title = "The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling",
abstract = "Interactions of myeloma cells with the bone marrow microenvironment lead to enhanced osteoclast recruitment and impaired osteoblast activity. Recent evidence revealed that the proteasome inhibitor bortezomib stimulates osteoblast differentiation, but the mechanisms are not fully elucidated. We hypothesised that bortezomib could influence osteoblastic differentiation via alteration of vitamin D signalling by blocking the proteasomal degradation of the vitamin D receptor (VDR). This is of clinical importance, as a high rate of vitamin D deficiency was reported in patients with myeloma. We performed cocultures of primary human mesenchymal stem cells (hMSCs) and human osteoblasts (hOBs) with myeloma cells, which resulted in an inhibition of the vitamin D-dependent differentiation of osteoblast precursors. Treatment with bortezomib led to a moderate increase in osteoblastic differentiation markers in hMSCs and hOBs. Importantly, this effect could be strikingly increased when vitamin D was added. Bortezomib led to enhanced nuclear VDR protein levels in hMSCs. Primary hMSCs transfected with a VDR luciferase reporter construct showed a strong increase in VDR signalling with bortezomib. In summary, stimulation of VDR signalling is a mechanism for the bortezomib-induced stimulation of osteoblastic differentiation. The data suggest that supplementation of vitamin D in patients with myeloma treated with bortezomib is crucial for optimal bone formation.",
keywords = "Base Sequence, Boronic Acids, Cell Differentiation, Cell Line, Tumor, Cells, Cultured, Coculture Techniques, Humans, Mesenchymal Stromal Cells, Multiple Myeloma, Osteoblasts, Osteocalcin, Osteoclasts, Osteopontin, Proteasome Inhibitors, Pyrazines, RNA, Messenger, Receptors, Calcitriol, Recombinant Proteins, Signal Transduction, Transfection, Up-Regulation, Vitamin D Deficiency",
author = "Kaiser, {Martin F} and Ulrike Heider and Maren Mieth and Chuanbing Zang and {von Metzler}, Ivana and Orhan Sezer",
note = "{\textcopyright} 2013 John Wiley & Sons A/S.",
year = "2013",
month = apr,
day = "1",
doi = "10.1111/ejh.12069",
language = "English",
volume = "90",
pages = "263--72",
journal = "EUR J HAEMATOL",
issn = "0902-4441",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - The proteasome inhibitor bortezomib stimulates osteoblastic differentiation of human osteoblast precursors via upregulation of vitamin D receptor signalling

AU - Kaiser, Martin F

AU - Heider, Ulrike

AU - Mieth, Maren

AU - Zang, Chuanbing

AU - von Metzler, Ivana

AU - Sezer, Orhan

N1 - © 2013 John Wiley & Sons A/S.

PY - 2013/4/1

Y1 - 2013/4/1

N2 - Interactions of myeloma cells with the bone marrow microenvironment lead to enhanced osteoclast recruitment and impaired osteoblast activity. Recent evidence revealed that the proteasome inhibitor bortezomib stimulates osteoblast differentiation, but the mechanisms are not fully elucidated. We hypothesised that bortezomib could influence osteoblastic differentiation via alteration of vitamin D signalling by blocking the proteasomal degradation of the vitamin D receptor (VDR). This is of clinical importance, as a high rate of vitamin D deficiency was reported in patients with myeloma. We performed cocultures of primary human mesenchymal stem cells (hMSCs) and human osteoblasts (hOBs) with myeloma cells, which resulted in an inhibition of the vitamin D-dependent differentiation of osteoblast precursors. Treatment with bortezomib led to a moderate increase in osteoblastic differentiation markers in hMSCs and hOBs. Importantly, this effect could be strikingly increased when vitamin D was added. Bortezomib led to enhanced nuclear VDR protein levels in hMSCs. Primary hMSCs transfected with a VDR luciferase reporter construct showed a strong increase in VDR signalling with bortezomib. In summary, stimulation of VDR signalling is a mechanism for the bortezomib-induced stimulation of osteoblastic differentiation. The data suggest that supplementation of vitamin D in patients with myeloma treated with bortezomib is crucial for optimal bone formation.

AB - Interactions of myeloma cells with the bone marrow microenvironment lead to enhanced osteoclast recruitment and impaired osteoblast activity. Recent evidence revealed that the proteasome inhibitor bortezomib stimulates osteoblast differentiation, but the mechanisms are not fully elucidated. We hypothesised that bortezomib could influence osteoblastic differentiation via alteration of vitamin D signalling by blocking the proteasomal degradation of the vitamin D receptor (VDR). This is of clinical importance, as a high rate of vitamin D deficiency was reported in patients with myeloma. We performed cocultures of primary human mesenchymal stem cells (hMSCs) and human osteoblasts (hOBs) with myeloma cells, which resulted in an inhibition of the vitamin D-dependent differentiation of osteoblast precursors. Treatment with bortezomib led to a moderate increase in osteoblastic differentiation markers in hMSCs and hOBs. Importantly, this effect could be strikingly increased when vitamin D was added. Bortezomib led to enhanced nuclear VDR protein levels in hMSCs. Primary hMSCs transfected with a VDR luciferase reporter construct showed a strong increase in VDR signalling with bortezomib. In summary, stimulation of VDR signalling is a mechanism for the bortezomib-induced stimulation of osteoblastic differentiation. The data suggest that supplementation of vitamin D in patients with myeloma treated with bortezomib is crucial for optimal bone formation.

KW - Base Sequence

KW - Boronic Acids

KW - Cell Differentiation

KW - Cell Line, Tumor

KW - Cells, Cultured

KW - Coculture Techniques

KW - Humans

KW - Mesenchymal Stromal Cells

KW - Multiple Myeloma

KW - Osteoblasts

KW - Osteocalcin

KW - Osteoclasts

KW - Osteopontin

KW - Proteasome Inhibitors

KW - Pyrazines

KW - RNA, Messenger

KW - Receptors, Calcitriol

KW - Recombinant Proteins

KW - Signal Transduction

KW - Transfection

KW - Up-Regulation

KW - Vitamin D Deficiency

U2 - 10.1111/ejh.12069

DO - 10.1111/ejh.12069

M3 - SCORING: Journal article

C2 - 23311753

VL - 90

SP - 263

EP - 272

JO - EUR J HAEMATOL

JF - EUR J HAEMATOL

SN - 0902-4441

IS - 4

ER -