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- Title
Indirubin-3′-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway.
- Authors
Choi, Sehee; Cha, Pu-Hyeon; Kim, Hyun-Yi; Choi, Kang-Yell
- Abstract
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. Small molecular approach to increase height growth: A compound that stimulates longitudinal bone growth could lead to safer treatments for children with short stature. Growth hormone treatments can normalize development in some children with growth hormone deficiency, but the side effects can be severe. Researchers led by Kang-Yell Choi at Yonsei University, Seoul, South Korea, have determined that chemical stimulation of a critical cell signaling pathway involving bone growth may offer a better approach for growing taller. Longitudinal growth of bones is driven by the proliferation and differentiation of cartilage cells in the growth plate. Choi and colleagues screened a chemical library and identified a compound derived from traditional Chinese herbs, which efficiently promotes this bone growth process in cultured cartilage cells and in the tibias of three-week-old mice. This compound appears safe, suggesting a potentially better avenue for promoting height growth.
- Publication
Experimental & Molecular Medicine EMM, 2019, Vol 51, Issue 9, pN.PAG
- ISSN
1226-3613
- Publication type
Article
- DOI
10.1038/s12276-019-0306-3