کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2781900 1153337 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PPARγ inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
PPARγ inhibits osteogenesis via the down-regulation of the expression of COX-2 and iNOS in rats
چکیده انگلیسی

Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated transcription factor, is considered as an anti-osteoblastic factor associated with adiposity and the elderly osteoporosis due to a defect in osteoblastogenesis. We have found that oral administration of PPARγ activator rosiglitazone decreased tibia BMD and serum ALP but left serum calcium and osteoclast marker C-terminal telopeptide unaffected. In addition, we examined the inhibitory mechanisms of PPARγ on the bone formation by using PPARγ activators ciglitazone and 15-deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2). Our data indicated that PPARγ ligands decreased both mineralized bone nodules and alkaline phosphatase (ALP) activities in cultured primary osteoblasts. Reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of bone morphogenetic protein-2 (BMP-2) and osteocalcin (OCN) was inhibited by ciglitizone and 15d-PGJ2. Furthermore, PPARγ ligands inhibited NF-κB associated downstream COX-2 and iNOS osteogenic signaling. The ultrasound (US)-induced elevation of COX-2 and iNOS expression and nitric oxide (NO) production were attenuated in the presence of PPARγ ligands. Furthermore, local administration of PPARγ ligands into the metaphysis of rat tibia decreased the bone volume in secondary spongiosa. These results suggest that the activation of PPARγ inhibits osteoblastic differentiation and the expression of several anabolic mediators involved in bone formation. These data may reflect osteoporosis and less bone formation in the aging people and patients treated with thiazolidinediones.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 41, Issue 4, October 2007, Pages 562–574
نویسندگان
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