C/EBP-α, involvement of a novel transcription factor in leptin-induced VCAM-1 production in mouse chondrocytes.
Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure. Here we show that leptin upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner. Mechanistically, leptin induces VCAM-1 promoter activity by increasing the expression of C/EBP-α and facilitating its binding to a newly identified element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory role of C/EBP-α on VCAM-1 expression. Finally, elevated plasma leptin level correlates to increased C/EBP-α and VCAM-1 production in chondrocytes from obese mice.
['Kang|Xia|X|', 'Xie|Qing-Yun|QY|', 'Zhou|Jing-Song|JS|', 'Zhang|Bo|B|', 'Liao|Dong-Fa|DF|', 'Wu|Hong-Hua|HH|', 'Zheng|Wei|W|', 'Pan|Xian-Ming|XM|', 'Quan|Yi|Y|']
D000818:Animals D001665:Binding Sites D022762:CCAAT-Enhancer-Binding Proteins D002478:Cells, Cultured D019902:Chondrocytes D006801:Humans D020738:Leptin D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009765:Obesity D061251:Primary Cell Culture D011401:Promoter Regions, Genetic D012333:RNA, Messenger D019010:Vascular Cell Adhesion Molecule-1
C/EBP-α VCAM-1 Leptin Osteoarthritis