Role of Lipocalin-type prostaglandin D synthase in experimental osteoarthritis
M Najar,etc Arthritis & Rheumatology,
ObjectiveLipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the formation of prostaglandin D2 (PGD2), which has important roles in inflammation and cartilage metabolism. The aim of this study was to investigate the role of L-PGDS in the pathogenesis of OA using an experimental mouse model.MethodsExperimental 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 MMP-13 and ADAMTS-5 was assessed by immunohistochemistry. Bone changes were determined by microcomputed tomography (µ-CT). Cartilage explants from L-PGDS-/- and WT mice (n = 6 per genotype) were treated with interleukin-1a (IL-1a) ex vivo , to evaluate proteoglycan degradation. Moreover, the effect of intra-articular injection of an adeno-associated virus (AAV) 2/5 encoding L-PGDS on OA progression was evaluated in WT mice (n = 9 per group).ResultsCompared 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-1a (P < 0.05). Intra-articular injection of AAV2/5 encoding L-PGDS attenuated the severity of DMM-induced OA-like changes in WT mice (P < 0.05). The level of L-PGDS was increased in OA tissues of WT mice (P < 0.05).ConclusionCollectively, these findings suggest a protective role of L-PGDS in OA, and therefore enhancing it level may constitute a promising therapeutic strategy.
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