Impact of VX-765 and VX-740 on chondrogenesis and inflammatory cytokine release in murine micromass cultures

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F25%3A00640010" target="_blank" >RIV/67985904:_____/25:00640010 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/25:00143233 RIV/62157124:16170/25:43882450

Výsledek na webu

<a href="https://www.tandfonline.com/doi/pdf/10.1080/03008207.2025.2539414?utm_source=clarivate&getft_integrator=clarivate" target="_blank" >https://www.tandfonline.com/doi/pdf/10.1080/03008207.2025.2539414?utm_source=clarivate&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/03008207.2025.2539414" target="_blank" >10.1080/03008207.2025.2539414</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Impact of VX-765 and VX-740 on chondrogenesis and inflammatory cytokine release in murine micromass cultures

Popis výsledku v původním jazyce

AimCaspase-1 inhibition is a promising option for degenerative joint diseases such as osteoarthritis, however, there is still a long way to go toward clinical use. One of the open challenges is associated with the non-inflammatory role of this caspase in the inflammatory environment as well as under physiological conditions. This study therefore focuses on two already pre-clinically tested caspase-1 inhibitors, VX-765 and VX-740, to specify their effects on chondrogenic cells.Material and methodsThe analysis was performed on mouse micromass cultures where chondrocyte differentiation, inflammatory cytokine release, and gene expression were examined.ResultsOur data indicate that the inhibitor VX-740 increases chondrogenesis, suggesting osteocalcin as a target molecule. In the inflammatory environment induced by IL-1 beta, there was an increase in chondrogenic nodules and partial compensation of differentiation for both investigated inhibitors. Morphological changes were not primarily due to changes in chondrogenic/osteogenic gene expression, but different levels of inflammatory molecules were found in the culture supernatant. While an increase in anti-inflammatory cytokine levels was observed with VX-765, a decrease in pro-inflammatory cytokines was recorded in the case of VX-740 treatment.ConclusionThe results demonstrate the differential effects of the caspase-1 inhibitors VX-765 and VX-740 on chondrogenic cell cultures and point to molecules that may be potential targets for use in the local treatment of osteoarthritis.

Název v anglickém jazyce

Impact of VX-765 and VX-740 on chondrogenesis and inflammatory cytokine release in murine micromass cultures

Popis výsledku anglicky

AimCaspase-1 inhibition is a promising option for degenerative joint diseases such as osteoarthritis, however, there is still a long way to go toward clinical use. One of the open challenges is associated with the non-inflammatory role of this caspase in the inflammatory environment as well as under physiological conditions. This study therefore focuses on two already pre-clinically tested caspase-1 inhibitors, VX-765 and VX-740, to specify their effects on chondrogenic cells.Material and methodsThe analysis was performed on mouse micromass cultures where chondrocyte differentiation, inflammatory cytokine release, and gene expression were examined.ResultsOur data indicate that the inhibitor VX-740 increases chondrogenesis, suggesting osteocalcin as a target molecule. In the inflammatory environment induced by IL-1 beta, there was an increase in chondrogenic nodules and partial compensation of differentiation for both investigated inhibitors. Morphological changes were not primarily due to changes in chondrogenic/osteogenic gene expression, but different levels of inflammatory molecules were found in the culture supernatant. While an increase in anti-inflammatory cytokine levels was observed with VX-765, a decrease in pro-inflammatory cytokines was recorded in the case of VX-740 treatment.ConclusionThe results demonstrate the differential effects of the caspase-1 inhibitors VX-765 and VX-740 on chondrogenic cell cultures and point to molecules that may be potential targets for use in the local treatment of osteoarthritis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])

Projekt

<a href="/cs/project/LUABA22019" target="_blank" >LUABA22019: Kaspáza-1 a chondrocyty: integrace výzkumu orientovaného na osteoartritidu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Connective Tissue Research

ISSN

0300-8207

e-ISSN

1607-8438

Svazek periodika

66

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

582-592

Kód UT WoS článku

001540178500001

EID výsledku v databázi Scopus

2-s2.0-105012203199