Antiosteogenic effect of arsenic trioxide, cholecalciferol, lovastatin or their combination in vitro
Апстракт
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.
Кључне речи:
heterotopic ossification / Hedgehog inhibitors / combination therapy / mesenchymal stem cellsИзвор:
Journal of the Serbian Chemical Society, 2019, 84, 9, 951-960Издавач:
- Srpsko hemijsko društvo, Beograd
DOI: 10.2298/JSC190304060G
ISSN: 0352-5139
WoS: 000489023300004
Scopus: 2-s2.0-85072950364
Институција/група
Tehnološko-metalurški fakultetTY - 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 . .