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Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro

Thumbnail
2019
4054.pdf (3.507Mb)
Authors
Gvozdenović-Jeremić, Jelena
Vert-Wong, Ekaterina
Mojović, Ljiljana
Article (Published version)
Metadata
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Abstract
Pathological formation of bone in non-skeletal soft tissues or heterotopic ossification (HO), for which there is currently no effective treatment, is considered to be mediated by activation of Hedgehog (Hh) signaling pathway. Moreover, the biochemical mechanism of this pathological process is not fully understood. Here, we tested the efficacy of three chemical inhibitors of the Hh signaling pathway, arsenic trioxide (ATO), lovastatin (Lov) and cholecalciferol (Vitamin D) to hamper differentiation of mesenchymal stem cells (MSC) into osteoblasts or osteogenesis. Each of the three Hh inhibitors potently decreased alkaline phosphatase activity, suggesting effective suppression of osteogenic activity in Hh-impaired MSC. Gene expression analysis revealed a significant reduction in mRNA levels of chief Hh signaling marker, Gli1, following administration of Hh small molecule inhibitors. A functional link between Hedgehog and osteogenesis in native MSC cells is further established in studies i...nvolving the mix of three Hh inhibitors acting at different checkpoints of the Hh signaling pathway. Thus, a combination of small molecule inhibitors of the Hh pathway at their lower concentrations could be a novel approach for HO prophylaxis with increased efficacy and potentially reduced side effects.

Keywords:
heterotopic ossification / Hedgehog inhibitors / combination therapy / mesenchymal stem cells
Source:
Journal of the Serbian Chemical Society, 2019, 84, 9, 951-960
Publisher:
  • Srpsko hemijsko društvo, Beograd

DOI: 10.2298/JSC190304060G

ISSN: 0352-5139

WoS: 000489023300004

Scopus: 2-s2.0-85072950364
[ Google Scholar ]
URI
http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4057
Collections
  • Radovi istraživača / Researchers’ publications (TMF)
Institution/Community
Tehnološko-metalurški fakultet
TY  - JOUR
AU  - Gvozdenović-Jeremić, Jelena
AU  - Vert-Wong, Ekaterina
AU  - Mojović, Ljiljana
PY  - 2019
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4057
AB  - Pathological formation of bone in non-skeletal soft tissues or heterotopic ossification (HO), for which there is currently no effective treatment, is considered to be mediated by activation of Hedgehog (Hh) signaling pathway. Moreover, the biochemical mechanism of this pathological process is not fully understood. Here, we tested the efficacy of three chemical inhibitors of the Hh signaling pathway, arsenic trioxide (ATO), lovastatin (Lov) and cholecalciferol (Vitamin D) to hamper differentiation of mesenchymal stem cells (MSC) into osteoblasts or osteogenesis. Each of the three Hh inhibitors potently decreased alkaline phosphatase activity, suggesting effective suppression of osteogenic activity in Hh-impaired MSC. Gene expression analysis revealed a significant reduction in mRNA levels of chief Hh signaling marker, Gli1, following administration of Hh small molecule inhibitors. A functional link between Hedgehog and osteogenesis in native MSC cells is further established in studies involving the mix of three Hh inhibitors acting at different checkpoints of the Hh signaling pathway. Thus, a combination of small molecule inhibitors of the Hh pathway at their lower concentrations could be a novel approach for HO prophylaxis with increased efficacy and potentially reduced side effects.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro
EP  - 960
IS  - 9
SP  - 951
VL  - 84
DO  - 10.2298/JSC190304060G
ER  - 
@article{
author = "Gvozdenović-Jeremić, Jelena and Vert-Wong, Ekaterina and Mojović, Ljiljana",
year = "2019",
abstract = "Pathological formation of bone in non-skeletal soft tissues or heterotopic ossification (HO), for which there is currently no effective treatment, is considered to be mediated by activation of Hedgehog (Hh) signaling pathway. Moreover, the biochemical mechanism of this pathological process is not fully understood. Here, we tested the efficacy of three chemical inhibitors of the Hh signaling pathway, arsenic trioxide (ATO), lovastatin (Lov) and cholecalciferol (Vitamin D) to hamper differentiation of mesenchymal stem cells (MSC) into osteoblasts or osteogenesis. Each of the three Hh inhibitors potently decreased alkaline phosphatase activity, suggesting effective suppression of osteogenic activity in Hh-impaired MSC. Gene expression analysis revealed a significant reduction in mRNA levels of chief Hh signaling marker, Gli1, following administration of Hh small molecule inhibitors. A functional link between Hedgehog and osteogenesis in native MSC cells is further established in studies involving the mix of three Hh inhibitors acting at different checkpoints of the Hh signaling pathway. Thus, a combination of small molecule inhibitors of the Hh pathway at their lower concentrations could be a novel approach for HO prophylaxis with increased efficacy and potentially reduced side effects.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro",
pages = "960-951",
number = "9",
volume = "84",
doi = "10.2298/JSC190304060G"
}
Gvozdenović-Jeremić, J., Vert-Wong, E.,& Mojović, L.. (2019). Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 84(9), 951-960.
https://doi.org/10.2298/JSC190304060G
Gvozdenović-Jeremić J, Vert-Wong E, Mojović L. Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro. in Journal of the Serbian Chemical Society. 2019;84(9):951-960.
doi:10.2298/JSC190304060G .
Gvozdenović-Jeremić, Jelena, Vert-Wong, Ekaterina, Mojović, Ljiljana, "Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro" in Journal of the Serbian Chemical Society, 84, no. 9 (2019):951-960,
https://doi.org/10.2298/JSC190304060G . .

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