توجه ! این یک نسخه آرشیو شده میباشد و در این حالت شما عکسی را مشاهده نمیکنید برای مشاهده کامل متن و عکسها بر روی لینک مقابل کلیک کنید : Adult Cartilage-Specific Peroxisome Proliferatore Activated Receptor Gamma Knockout Mice Exhibit the Spontaneous Osteoarthritis Phenotype

محمد بهبهانی
04-10-2013, 02:53 PM
Osteoarthritis (OA) is an age-related progressive degenerative joint disease. Peroxisome proliferatoreactivated
receptor gamma (PPARg), a transcription factor, is suggested as an attractive
therapeutic target to counteract degradative mechanisms associated with OA. Studies suggest that
activation of PPARg 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
PPARg-independent effects, the specific in vivo function of PPARg in cartilage homeostasis and OA
remains largely unknown. Herein, we describe the in vivo role of PPARg in OA using cartilage-specific
PPARg knockout (KO) mice generated using the Cre-lox system. Adult PPARg 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 metalloproteinaseegenerated aggrecan and type II collagen neoepitopes
(VDIPEN and C1-2C). We demonstrate that PPARg-deficient articular cartilage exhibits
elevated expression of the additional catabolic factors hypoxia-inducible factor-2a, 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, PPARg is a critical regulator of
cartilage health, the lack of which leads to an accelerated spontaneous OA phenotype. (Am J Pathol
2013, 182: 1099e1106; Elsevier: Article Locator (http://dx.doi.org/10.1016/j.ajpath.2012.12.012))