Role of Lipocalin‐Type Prostaglandin D Synthase in Experimental Osteoarthritis. Issue 9 (30th July 2020)

• Record Type: Journal Article
• Authors: Najar, Mehdi; Ouhaddi, Yassine; Paré, Frédéric; Lussier, Bertrand; Urade, Yoshihiro; Kapoor, Mohit; Pelletier, Jean‐Pierre; Martel‐Pelletier, Johanne; Benderdour, Mohamed; Fahmi, Hassan
• Is Part Of: Arthritis & rheumatology. Volume 72:Issue 9(2020)
• Page Start: 1524
• Page End: 1533
• Publication Date: 2020-07-30
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.41297
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : Objective: Lipocalin‐type prostaglandin D synthase (L‐PGDS) catalyzes the formation of prostaglandin D2 (PGD2 ), which has important roles in inflammation and cartilage metabolism. We undertook this study to investigate the role of L‐PGDS in the pathogenesis of osteoarthritis (OA) using an experimental mouse model. Methods: Experimental OA was induced in wild‐type (WT) and L‐PGDS–deficient (L‐PGDS −/− ) mice (n = 10 per genotype) by destabilization of the medial meniscus (DMM). Cartilage degradation was evaluated by histology. The expression of matrix metalloproteinase 13 (MMP‐13) and ADAMTS‐5 was assessed by immunohistochemistry. Bone changes were determined by micro–computed tomography. Cartilage explants from L‐PGDS −/− and WT mice (n = 6 per genotype) were treated with interleukin‐1α (IL‐1α) ex vivo in order to evaluate proteoglycan degradation. Moreover, the effect of intraarticular injection of a recombinant adeno‐associated virus type 2/5 (rAAV2/5) encoding L‐PGDS on OA progression was evaluated in WT mice (n = 9 per group). Results: Compared to WT mice, L‐PGDS −/− mice had exacerbated cartilage degradation and enhanced expression of MMP‐13 and ADAMTS‐5 ( P < 0.05). Furthermore, L‐PGDS −/− mice displayed increased synovitis and subchondral bone changes ( P < 0.05). Cartilage explants from L‐PGDS −/− mice showed enhanced proteoglycan degradation following treatment with IL‐1α ( P < 0.05). Intraarticular injection of rAAV2/5 encoding L‐PGDS attenuated the severity of DMM‐induced OA‐like changes in WT mice ( P < 0.05). The L‐PGDS level was increased in OA tissues of WT mice ( P < 0.05). Conclusion: Collectively, these findings suggest a protective role of L‐PGDS in OA, and therefore enhancing levels of L‐PGDS may constitute a promising therapeutic strategy.