Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration
Summary
Aging or injury to the joints can lead to cartilage degeneration and osteoarthritis (OA), for which there are limited effective treatments. We found that expression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH) is increased in the articular cartilage of aged or injured mice. Both systemic and local inhibition of 15-PGDH with a small-molecule inhibitor (PGDHi) led to regeneration of articular cartilage and reduction in OA-associated pain. Using single-cell RNA-sequencing and multiplex
Content
# Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration
*Published: 2026 Mar 5*
Aging or injury to the joints can lead to cartilage degeneration and
osteoarthritis (OA), for which there are limited effective treatments. We found
that expression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH) is increased
in the articular cartilage of aged or injured mice. Both systemic and local
inhibition of 15-PGDH with a small-molecule inhibitor (PGDHi) led to
regeneration of articular cartilage and reduction in OA-associated pain. Using
single-cell RNA-sequencing and multiplexed immunofluorescence imaging of
cartilage, we identified the major chondrocyte subpopulations. Inhibition of
15-PGDH decreased hypertrophic-like chondrocytes expressing 15-PGDH and
increased extracellular matrix-synthesizing articular chondrocytes. Cartilage
regeneration appears to occur through gene expression changes in preexisting
chondrocytes, rather than stem or progenitor cell proliferation. 15-PGDH
inhibition could be a potential disease-modifying and regenerative approach for
osteoarthritis.
DOI: 10.1126/science.adx6649