title: Adult cartilage-specific peroxisome proliferator-activated receptor gamma knockout mice exhibit the spontaneous osteoarthritis phenotype.
abstract: Osteoarthritis (OA) is an age-related progressive degenerative joint disease. Peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor, is suggested as an attractive therapeutic target to counteract degradative mechanisms associated with OA. Studies suggest that activation of PPARγ by its agonists can reduce the synthesis of OA catabolic and inflammatory factors and the development of cartilage lesions in OA animal models. Because these agonists impart several PPARγ-independent effects, the specific in vivo function of PPARγ in cartilage homeostasis and OA remains largely unknown. Herein, we describe the in vivo role of PPARγ in OA using cartilage-specific PPARγ knockout (KO) mice generated using the Cre-lox system. Adult PPARγ KO mice exhibited a spontaneous OA phenotype associated with enhanced cartilage degradation, hypocellularity, synovial and cartilage fibrosis, synovial inflammation, mononuclear cell influx in the synovium, and increased expression of catabolic factors, including matrix metalloproteinase-13, accompanied by an increase in staining for matrix metalloproteinase-generated aggrecan and type II collagen neoepitopes (VDIPEN and C1-2C). We demonstrate that PPARγ-deficient articular cartilage exhibits elevated expression of the additional catabolic factors hypoxia-inducible factor-2α, syndecan-4, and a disintegrin and metalloproteinase with thrombospondin motifs 5 and of the inflammatory factors cyclooxygenase-2 and inducible nitric oxide synthase. In conclusion, PPARγ is a critical regulator of cartilage health, the lack of which leads to an accelerated spontaneous OA phenotype.
authors: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre.
authors: Faezeh
authors: F
authors: Vasheghani
authors: Roxana
authors: R
authors: Monemdjou
authors: Hassan
authors: H
authors: Fahmi
authors: Yue
authors: Y
authors: Zhang
authors: Gemma
authors: G
authors: Perez
authors: Meryem
authors: M
authors: Blati
authors: René
authors: R
authors: St-Arnaud
authors: Jean-Pierre
authors: JP
authors: Pelletier
authors: Frank
authors: F
authors: Beier
authors: Johanne
authors: J
authors: Martel-Pelletier
authors: Mohit
authors: M
authors: Kapoor
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology*; D005355:Fibrosis; D017353:Gene Deletion; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D047495:PPAR gamma / Q000172:deficiency* / Q000378:metabolism; D010641:Phenotype; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D047495:PPAR gamma