研究团队发现15-羟基前列腺素脱氢酶（15-PGDH）在老年或损伤小鼠关节软骨中的表达增加。用小分子抑制剂（PGDHi）全身和局部抑制15-PGDH可导致关节软骨再生和oa相关疼痛减轻。利用单细胞RNA测序和软骨的多重免疫荧光成像，研究团队确定了主要的软骨细胞亚群。抑制15-PGDH可减少表达15-PGDH的肥大样软骨细胞，增加细胞外基质合成关节软骨细胞。软骨再生似乎是通过预先存在的软骨细胞的基因表达变化而发生的，而不是干细胞或祖细胞增殖。15-PGDH抑制可能是骨关节炎的一种潜在的疾病改善和再生方法。
据悉，关节的老化或损伤可导致软骨变性和骨关节炎（OA），目前有效的治疗方法有限。
附：英文原文
Title: Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration
Author: Mamta Singla, Yu Xin Wang, Elena Monti, Yudhishtar Bedi, Pranay Agarwal, Shiqi Su, Sara Ancel, Maiko Hermsmeier, Nitya Devisetti, Akshay Pandey, Mohsen Afshar Bakooshli, Adelaida R. Palla, Stuart Goodman, Helen M Blau, Nidhi Bhutani
Issue&Volume: 2025-11-27
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.
DOI: adx6649
Source: https://www.science.org/doi/10.1126/science.adx6649