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Exacerbation of Aging‐Associated and Instability‐Induced Murine Osteoarthritis With Deletion of D Prostanoid Receptor 1, a Prostaglandin D 2 Receptor
Author(s) -
Ouhaddi Yassine,
Nebbaki SarahSalwa,
Habouri Lauris,
Afif Hassan,
Lussier Bertrand,
Kapoor Mohit,
Narumiya Shuh,
Pelletier JeanPierre,
MartelPelletier Johanne,
Benderdour Mohamed,
Fahmi Hassan
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40160
Subject(s) - prostanoid , osteoarthritis , cartilage , medicine , agonist , endocrinology , receptor , pathogenesis , chemistry , pathology , anatomy , alternative medicine
Objective D prostanoid receptor 1 (DP1), a receptor for prostaglandin D 2 , plays important roles in inflammation and cartilage metabolism. However, its role in the pathogenesis of osteoarthritis (OA) remains unknown. This study was undertaken to explore the roles of DP1 in the development of OA in murine models and to evaluate the efficacy of a DP1 selective agonist in the treatment of OA. Methods The development of aging‐associated OA and destabilization of the medial meniscus (DMM)–induced OA was compared between DP1‐deficient (DP1 −/− ) and wild‐type (WT) mice. The progression of OA was assessed by histology, immunohistochemistry, and micro–computed tomography. Cartilage explants from DP1 −/− and WT mice were treated with interleukin‐1α (IL‐1α) ex vivo, to evaluate proteoglycan degradation. The effect of intraperitoneal administration of the DP1 selective agonist BW245C on OA progression was evaluated in WT mice. Results Compared to WT mice, DP1 −/− mice had exacerbated cartilage degradation in both models of OA, and this was associated with increased expression of matrix metalloproteinase 13 and ADAMTS‐5. In addition, DP1 −/− mice demonstrated enhanced subchondral bone changes. Cartilage explants from DP1 −/− mice showed enhanced proteoglycan degradation following treatment with IL‐1α. Intraperitoneal injection of BW245C attenuated the severity of DMM‐induced cartilage degradation and bony changes in WT mice. Conclusion These findings indicate a critical role for DP1 signaling in OA pathogenesis. Modulation of the functions of DP1 may constitute a potential therapeutic target for the development of novel OA treatments.