Role of Lipocalin-type prostaglandin D synthase in experimental osteoarthritis.

Authors：Najar, Mehdi; Ouhaddi, Yassine; Pare, Frederic; Lussier, Bertrand; Urade, Yoshihiro; Kapoor, Mohit; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Benderdour, Mohamed; Fahmi, Hassan

Source：Arthritis & Rheumatology, 2020.

DOI：10.1002/art.41297

OBJECTIVE: Lipocalin-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. 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 MMP-13 and ADAMTS-5 was assessed by immunohistochemistry. Bone changes were determined by microcomputed tomography (micro-CT). Cartilage explants from L-PGDS-/- and WT mice (n = 6 per genotype) were treated with interleukin-1alpha (IL-1alpha) 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). 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-1alpha (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). CONCLUSION: Collectively, these findings suggest a protective role of L-PGDS in OA, and therefore enhancing it level may constitute a promising therapeutic strategy.

• Institution
  University of Montreal; university of tokyo