Research ArticleOsteoarthritis

Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis

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Science Translational Medicine  10 Feb 2021:
Vol. 13, Issue 580, eaau8491
DOI: 10.1126/scitranslmed.aau8491

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An antidepressant for arthritis?

Pathological chondrocyte hypertrophy contributes to osteoarthritis (OA), a degenerative disease of the cartilage and bone. Carlson et al. studied the role of G protein–coupled receptor kinase 2 (GRK2), which is linked to cardiac hypertrophy, in OA. GRK2 was elevated in chondrocytes in mouse models of OA and in injured human cartilage, and genetic deletion of GRK2 decreased OA progression in mice. Treating chondrocytes with the antidepressant paroxetine, which inhibits GRK2, blunted disease progression and chondrocyte hypertrophy in mice in vivo and human OA cartilage ex vivo. Results show how repurposing paroxetine could have therapeutic effects for joint degeneration.

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