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• W3019728532 abstract "Objective Lipocalin‐type prostaglandin D synthase (L‐ PGDS ) catalyzes the formation of prostaglandin D 2 ( PGD 2 ), 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 (r AAV 2/5) 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 r AAV 2/5 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." @default.
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• W3019728532 date "2020-07-30" @default.
• W3019728532 modified "2023-10-16" @default.
• W3019728532 title "Role of Lipocalin‐Type Prostaglandin D Synthase in Experimental Osteoarthritis" @default.
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• W3019728532 doi "https://doi.org/10.1002/art.41297" @default.
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