WNK2 variants associated with familial osteoarthritis alter the chondrocyte response to hyperosmotic stress
Authors' conclusion
Our data indicate elevated WNK2 signalling is associated with heightened susceptibility to OA.
Study context
- Population
- Independent families with dominant inheritance of osteoarthritis (OA); normal and osteoarthritic human and mouse tissue; immortalised and primary human chondrocytes
- Comparison
- Wild type vs OA-associated variant WNK2 in chondrocytes under hyperosmotic stress
Methodological detailsfamily-based genomic analysis, immunohistochemistry, overexpression and loss-of-function experiments, transcriptomic analyses
- Family-based genomic analysis
- Immunohistochemistry
- Overexpression and loss-of-function experiments
- Transcriptomic analyses
Main finding
As reported in the abstract
- Novel coding variants of WNK2 associated with familial erosive hand OA and foot OA
- WNK2 expressed in chondrocytes; expression highly elevated in end-stage human and mouse OA joints
- Under hyperosmotic stress, chondrocytes initiate a remodelling response, altering expression of anabolic and catabolic genes and pathways
- Elevated WNK2 expression plus hyperosmotic stress promotes a WNK2-dependent OA-associated transcriptional response, exacerbated by the OA-associated WNK2 variants
Original publication
WNK2 variants associated with familial osteoarthritis alter the chondrocyte response to hyperosmotic stress. RMD Open. Published 1 July 2025. doi:10.
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