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PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption

Osteogenesis is an orchestrated process regulated by osteoclastogenesis and osteoblastogenesis. Excessive osteoclastogenesis causes bone diseases, such as osteoporosis. Although a few drugs are effective in osteoporosis treatment, these drugs lead to side effects, including cellulitis, flatulence, a...

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Autores principales: Cho, Eunjin, Chen, Zhihao, Lee, Jinkyung, Lee, Sunwoo, Lee, Tae-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767254/
https://www.ncbi.nlm.nih.gov/pubmed/31540026
http://dx.doi.org/10.3390/molecules24183346
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author Cho, Eunjin
Chen, Zhihao
Lee, Jinkyung
Lee, Sunwoo
Lee, Tae-Hoon
author_facet Cho, Eunjin
Chen, Zhihao
Lee, Jinkyung
Lee, Sunwoo
Lee, Tae-Hoon
author_sort Cho, Eunjin
collection PubMed
description Osteogenesis is an orchestrated process regulated by osteoclastogenesis and osteoblastogenesis. Excessive osteoclastogenesis causes bone diseases, such as osteoporosis. Although a few drugs are effective in osteoporosis treatment, these drugs lead to side effects, including cellulitis, flatulence, and hypocalcemia. In this study, we reported a 2-(N-Phenylmethylsulfonamido)-N-(2-(phenylthio)phenyl)propanamide (PSTP) compound, PSTP-3,5-Me, as a potential therapeutic agent for osteoporosis. Mouse bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts by receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of PSTP-3,5-Me. PSTP-3,5-Me inhibited osteoclast differentiation by reduced tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and suppressed the expression of osteoclast marker genes, such as cathepsin K (Ctsk) and TRAP (Acp5). We investigated signaling pathways mediated by RANKL and its receptor, RANK, and found that PSTP-3,5-Me inhibits nucleus translocation of nuclear factor of activated T cell cytoplasmic-1 (NFATc1). Moreover, PSTP-3,5-Me inhibited F-actin ring formation and mineral resorption. Overall, our data suggests that PSTP-3,5-Me attenuates osteoclast differentiation by blocking the activation of NFATc1.
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spelling pubmed-67672542019-10-02 PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption Cho, Eunjin Chen, Zhihao Lee, Jinkyung Lee, Sunwoo Lee, Tae-Hoon Molecules Article Osteogenesis is an orchestrated process regulated by osteoclastogenesis and osteoblastogenesis. Excessive osteoclastogenesis causes bone diseases, such as osteoporosis. Although a few drugs are effective in osteoporosis treatment, these drugs lead to side effects, including cellulitis, flatulence, and hypocalcemia. In this study, we reported a 2-(N-Phenylmethylsulfonamido)-N-(2-(phenylthio)phenyl)propanamide (PSTP) compound, PSTP-3,5-Me, as a potential therapeutic agent for osteoporosis. Mouse bone marrow-derived macrophages (BMMs) were differentiated into osteoclasts by receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of PSTP-3,5-Me. PSTP-3,5-Me inhibited osteoclast differentiation by reduced tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and suppressed the expression of osteoclast marker genes, such as cathepsin K (Ctsk) and TRAP (Acp5). We investigated signaling pathways mediated by RANKL and its receptor, RANK, and found that PSTP-3,5-Me inhibits nucleus translocation of nuclear factor of activated T cell cytoplasmic-1 (NFATc1). Moreover, PSTP-3,5-Me inhibited F-actin ring formation and mineral resorption. Overall, our data suggests that PSTP-3,5-Me attenuates osteoclast differentiation by blocking the activation of NFATc1. MDPI 2019-09-14 /pmc/articles/PMC6767254/ /pubmed/31540026 http://dx.doi.org/10.3390/molecules24183346 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cho, Eunjin
Chen, Zhihao
Lee, Jinkyung
Lee, Sunwoo
Lee, Tae-Hoon
PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
title PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
title_full PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
title_fullStr PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
title_full_unstemmed PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
title_short PSTP-3,5-Me Inhibits Osteoclast Differentiation and Bone Resorption
title_sort pstp-3,5-me inhibits osteoclast differentiation and bone resorption
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767254/
https://www.ncbi.nlm.nih.gov/pubmed/31540026
http://dx.doi.org/10.3390/molecules24183346
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