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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

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])

Project

<a href="/en/project/LUABA22019" target="_blank" >LUABA22019: Caspase-1 and chondrocytes: integration of osteoarthritis oriented research</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Connective Tissue Research

ISSN

0300-8207

e-ISSN

1607-8438

Volume of the periodical

66

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

582-592

UT code for WoS article

001540178500001

EID of the result in the Scopus database

2-s2.0-105012203199