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Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway

Researchers have shown increased interest in determining what stimulates height. Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. However, the current approach for height enhancement is limited to growth hormone treatment,...

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Autores principales: Choi, Sehee, Cha, Pu-Hyeon, Kim, Hyun-Yi, Choi, Kang-Yell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802626/
https://www.ncbi.nlm.nih.gov/pubmed/31515471
http://dx.doi.org/10.1038/s12276-019-0306-3
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author Choi, Sehee
Cha, Pu-Hyeon
Kim, Hyun-Yi
Choi, Kang-Yell
author_facet Choi, Sehee
Cha, Pu-Hyeon
Kim, Hyun-Yi
Choi, Kang-Yell
author_sort Choi, Sehee
collection PubMed
description Researchers have shown increased interest in determining what stimulates height. Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. However, the current approach for height enhancement is limited to growth hormone treatment, which often results in side effects and clinical failure and is costly. Although recent studies have indicated the importance of paracrine signals in the growth plate for longitudinal bone growth, height-stimulating agents targeting the signaling pathways involved in growth plate maturation remain unavailable in the clinic. The Wnt/β-catenin pathway plays a major role in the maturation of growth plate chondrocytes. In this study, by using an ex vivo tibial culture system, we identified indirubin-3′-oxime (I3O) as a compound capable of enhancing longitudinal bone growth. I3O promoted chondrocyte proliferation and differentiation via activation of the Wnt/β-catenin pathway in vitro. Intraperitoneal injection of I3O in adolescent mice increased growth plate height along with incremental chondrocyte maturation. I3O promoted tibial growth without significant adverse effects on bone thickness and articular cartilage. Therefore, I3O could be a potential therapeutic agent for increasing height in children with growth retardation.
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spelling pubmed-68026262019-10-29 Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway Choi, Sehee Cha, Pu-Hyeon Kim, Hyun-Yi Choi, Kang-Yell Exp Mol Med Article Researchers have shown increased interest in determining what stimulates height. Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. However, the current approach for height enhancement is limited to growth hormone treatment, which often results in side effects and clinical failure and is costly. Although recent studies have indicated the importance of paracrine signals in the growth plate for longitudinal bone growth, height-stimulating agents targeting the signaling pathways involved in growth plate maturation remain unavailable in the clinic. The Wnt/β-catenin pathway plays a major role in the maturation of growth plate chondrocytes. In this study, by using an ex vivo tibial culture system, we identified indirubin-3′-oxime (I3O) as a compound capable of enhancing longitudinal bone growth. I3O promoted chondrocyte proliferation and differentiation via activation of the Wnt/β-catenin pathway in vitro. Intraperitoneal injection of I3O in adolescent mice increased growth plate height along with incremental chondrocyte maturation. I3O promoted tibial growth without significant adverse effects on bone thickness and articular cartilage. Therefore, I3O could be a potential therapeutic agent for increasing height in children with growth retardation. Nature Publishing Group UK 2019-09-12 /pmc/articles/PMC6802626/ /pubmed/31515471 http://dx.doi.org/10.1038/s12276-019-0306-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Choi, Sehee
Cha, Pu-Hyeon
Kim, Hyun-Yi
Choi, Kang-Yell
Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway
title Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway
title_full Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway
title_fullStr Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway
title_full_unstemmed Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway
title_short Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway
title_sort indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the wnt/β-catenin pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802626/
https://www.ncbi.nlm.nih.gov/pubmed/31515471
http://dx.doi.org/10.1038/s12276-019-0306-3
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