Viudes-Sarrión, N., Castro-Viñuelas, R., Vaes, N., Blain, E.J.  ORCID: https://orcid.org/0000-0001-8944-4254, Lories, R.J. and Jonkers, I.
2026.
Interplay between canonical Wnt signaling and α5β1 integrins modulates mechanoresponse in human articular cartilage.
Osteoarthritis and Cartilage
10.1016/j.joca.2026.08.007
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Abstract
Objectives: Mechanical cues are essential for cartilage homeostasis, yet their interaction with molecular pathways dysregulated in osteoarthritis (OA) remains poorly understood. Canonical Wnt signalling regulates cartilage biology and cell–matrix interactions, but its role in integrin-dependent mechanoregulation is unclear. This study investigated how Wnt activation affects chondrocyte responses to physiological mechanical loading, focusing on α5β1 integrin and cytoskeletal organisation. Methods: Human cartilage explants from non-OA and OA donors were subjected to short-term physiological cyclic compression. Canonical Wnt signalling was activated with CHIR99021, and α5β1 integrins were blocked with ATN-161 during loading. Chondrocyte responses were assessed by mechanoresponsive and matrix-related gene expression, α5β1 complex formation using proximity ligation assay, and F-actin organisation by confocal microscopy. Results: OA chondrocytes exhibited increased ITGA5 and ITGB1 but reduced ITGA10 expression. In non-OA cartilage, Wnt activation increased ITGB1 expression and α5β1 complex formation, while loading further enhanced ITGA5 and ITGB1 transcription under Wnt-activated conditions. Under control conditions, loading induced mechanoresponsive and anabolic gene expression, whereas these responses were attenuated by Wnt activation and partially restored by α5β1 blockade. Mechanical loading promoted cortical F-actin reorganisation across cartilage zones irrespective of disease status or treatment. Wnt activation did not induce distinct cytoskeletal phenotypes under loading, and load-induced actin remodelling remained comparable between groups. Conclusions: These findings identify α5β1 integrin as a key mediator of Wnt-driven chondrocyte mechanoresponsiveness. Although loading consistently promoted cortical F-actin reorganisation, Wnt-associated changes in load responsiveness were primarily mediated through integrin-dependent mechanisms rather than major alterations in actin organisation, highlighting integrin signalling as a potential therapeutic target in OA.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Biosciences |
| Additional Information: | RRS policy applied |
| Publisher: | Elsevier |
| ISSN: | 1063-4584 |
| Date of First Compliant Deposit: | 24 August 2026 |
| Date of Acceptance: | 13 August 2026 |
| Last Modified: | 24 Aug 2026 14:15 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/189145 |
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