Vesela, Barbora and Dadakova, Katerina and Holomkova, Katerina and Blecha, Corina and Obratilova, Natalia and Graessel, Susanne and Matalova, Eva (2025) Impact of VX-765 and VX-740 on chondrogenesis and inflammatory cytokine release in murine micromass cultures. CONNECTIVE TISSUE RESEARCH, 66 (6). pp. 582-592. ISSN 0300-8207, 1607-8438
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OSTEOARTHRITIS; CARTILAGE; OSTEOCALCIN; ACTIVATION; INHIBITOR; Pralnacasan; Belnacasan; inflammatory caspases; cartilage; osteoarthritis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Sep 2026 08:17 |
| Last Modified: | 23 Sep 2026 08:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67171 |
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