Lithium rescues cultured rat metatarsals from dexamethasone-induced growth failure

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F24%3A10479867" target="_blank" >RIV/00064203:_____/24:10479867 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/24:10479867

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.EugFcQngU" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.EugFcQngU</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41390-024-03192-6" target="_blank" >10.1038/s41390-024-03192-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lithium rescues cultured rat metatarsals from dexamethasone-induced growth failure

Popis výsledku v původním jazyce

BACKGROUND: Glucocorticoids are commonly used in children with different chronic diseases. Growth failure represents a so far untreatable undesired side-effect. As lithium chloride (LiCl) is known to induce cell renewal in various tissues, we hypothesized that LiCl may prevent glucocorticoid-induced growth failure. METHODS: We monitored growth of fetal rat metatarsals cultured ex-vivo with dexamethasone and/or LiCl, while molecular mechanisms were explored through RNA sequencing by implementing the differential gene expression and gene set analysis. Quantification of β-catenin in human growth plate cartilage cultured with dexamethasone and/or LiCl was added for verification. RESULTS: After 14 days of culture, the length of dexamethasone-treated fetal rat metatarsals increased by 1.4 +- 0.2 mm compared to 2.4 +- 0.3 mm in control bones (p &lt; 0.001). The combination of LiCl and dexamethasone led to bone length increase of 1.9 +- 0.3 mm (p &lt; 0.001 vs. dexamethasone alone). By adding lithium, genes for cell cycle and Wnt/β-catenin, Hedgehog and Notch signaling, were upregulated compared to dexamethasone alone group. CONCLUSIONS: LiCl has the potential to partially rescue from dexamethasone-induced bone growth impairment in an ex vivo model. Transcriptomics identified cell renewal and proliferation as candidates for the underlying mechanisms. Our observations may open up the development of a new treatment strategy for bone growth disorders. IMPACT: LiCl is capable to prevent glucocorticoid-induced growth failure in rat metatarsals in vitro. The accompanying drug-induced transcriptomic changes suggested cell renewal and proliferation as candidate underlying mechanisms. Wnt/beta-catenin pathway could be one of those novel mechanisms.

Název v anglickém jazyce

Lithium rescues cultured rat metatarsals from dexamethasone-induced growth failure

Popis výsledku anglicky

BACKGROUND: Glucocorticoids are commonly used in children with different chronic diseases. Growth failure represents a so far untreatable undesired side-effect. As lithium chloride (LiCl) is known to induce cell renewal in various tissues, we hypothesized that LiCl may prevent glucocorticoid-induced growth failure. METHODS: We monitored growth of fetal rat metatarsals cultured ex-vivo with dexamethasone and/or LiCl, while molecular mechanisms were explored through RNA sequencing by implementing the differential gene expression and gene set analysis. Quantification of β-catenin in human growth plate cartilage cultured with dexamethasone and/or LiCl was added for verification. RESULTS: After 14 days of culture, the length of dexamethasone-treated fetal rat metatarsals increased by 1.4 +- 0.2 mm compared to 2.4 +- 0.3 mm in control bones (p &lt; 0.001). The combination of LiCl and dexamethasone led to bone length increase of 1.9 +- 0.3 mm (p &lt; 0.001 vs. dexamethasone alone). By adding lithium, genes for cell cycle and Wnt/β-catenin, Hedgehog and Notch signaling, were upregulated compared to dexamethasone alone group. CONCLUSIONS: LiCl has the potential to partially rescue from dexamethasone-induced bone growth impairment in an ex vivo model. Transcriptomics identified cell renewal and proliferation as candidates for the underlying mechanisms. Our observations may open up the development of a new treatment strategy for bone growth disorders. IMPACT: LiCl is capable to prevent glucocorticoid-induced growth failure in rat metatarsals in vitro. The accompanying drug-induced transcriptomic changes suggested cell renewal and proliferation as candidate underlying mechanisms. Wnt/beta-catenin pathway could be one of those novel mechanisms.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30209 - Paediatrics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pediatric Research

ISSN

0031-3998

e-ISSN

1530-0447

Svazek periodika

96

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

952-963

Kód UT WoS článku

001209609200003

EID výsledku v databázi Scopus

2-s2.0-85191736146