Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration

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.

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Publication Details

Journal
Science
Published
2025-11-27
DOI
https://doi.org/10.1126/science.adx6649
Citations
3
Primary Topic
Osteoarthritis Treatment and Mechanisms
Type
article
Field-Weighted Citation Impact
5.00
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article

Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration

Elena Monti, Maiko Hermsmeier, Stuart B. Goodman, Adelaida R. Palla et al.
3 citations
Science
Osteoarthritis Treatment and Mechanisms
5.00
article

Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration

Elena Monti, Maiko Hermsmeier, Stuart B. Goodman, Adelaida R. Palla, Mohsen Afshar Bakooshli, Pranay Agarwal, Shiqi Su, Mamta Singla, Yudhishtar S. Bedi, Yu Xin Wang, Sara Ancel, Helen M. Blau, Nitya Devisetti, Akshay Pandey, Nidhi Bhutani
article en
3 citations

Abstract

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.

ScienceVol. 391(6789)
Discovery Institute (US), Stanford University (US), Baxter (United States) (US)
Openalex Percentile: Top 4%
Osteoarthritis Treatment and Mechanisms
5.00
DOISourceOpenAlex
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