Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration - PubMed

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Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration - PubMed 
 Actions . 2025 Nov 27:eadx6649. doi: 10.1126/science.adx6649. Online ahead of print. Yu Xin Wang   #   2   3   4 ,  Elena Monti   2 ,  Yudhishtar Bedi   1 ,  Pranay Agarwal   1 ,  Shiqi Su   3 ,  Sara Ancel   3 ,  Maiko Hermsmeier   1 ,  Nitya Devisetti   1 ,  Akshay Pandey   1 ,  Mohsen Afshar Bakooshli   2 ,  Adelaida R Palla   2 ,  Stuart Goodman   1 ,  Helen M Blau   2 ,  Nidhi Bhutani   1 Affiliations PMID: 41308124 DOI: 10.1126/science.adx6649 Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration Mamta Singla  et al. Science . 2025 . 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 pre-existing chondrocytes, rather than stem or progenitor cell proliferation. 15-PGDH inhibition could be a potential disease-modifying and regenerative approach for osteoarthritis. PubMed Disclaimer Similar articles NFATc1 marks articular cartilage progenitors and negatively determines articular chondrocyte differentiation. Zhang F, Wang Y, Zhao Y, Wang M, Zhou B, Zhou B, Ge X. Zhang F, et al. Elife. 2023 Feb 15;12:e81569. doi: 10.7554/eLife.81569. Elife. 2023. PMID: 36790146 Free PMC article. Shoulder Arthrogram. Roberts CC, Escobar E. Roberts CC, et al. 2025 Sep 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. 2025 Sep 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 35593869 Free Books & Documents. In vitro and in vivo delivery of mRNA to joint cells using polymeric nanoparticles. Pontes AP, Rios JL, Rijker M, Warmink K, Gudi S, Conceição F, Meij B, Welting TJM, Teixeira LM, Rip J, Creemers LB. Pontes AP, et al. Acta Biomater. 2025 Aug;202:418-434. doi: 10.1016/j.actbio.2025.06.039. Epub 2025 Jun 24. Acta Biomater. 2025. PMID: 40570942 Clinical and cost-effectiveness of autologous chondrocyte implantation for cartilage defects in knee joints: systematic review and economic evaluation. Clar C, Cummins E, McIntyre L, Thomas S, Lamb J, Bain L, Jobanputra P, Waugh N. Clar C, et al. Health Technol Assess. 2005 Dec;9(47):iii-iv, ix-x, 1-82. doi: 10.3310/hta9470. Health Technol Assess. 2005. PMID: 16336842 Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. Mistry H, Connock M, Pink J, Shyangdan D, Clar C, Royle P, Court R, Biant LC, Metcalfe A, Waugh N. Mistry H, et al. Health Technol Assess. 2017 Feb;21(6):1-294. doi: 10.3310/hta21060. Health Technol Assess. 2017. PMID: 28244303 Free PMC article. LinkOut - more resources Full Text Sources Atypon Miscellaneous NCI CPTAC Assay Portal