NF-kappaB regulates Lef1 gene expression in chondrocytes.
The relation of Wnt/beta-catenin signaling to osteoarthritis progression has been revealed with little information on the underlying molecular mechanism. In this study we found overexpression of Lef1 in cartilage tissue of osteoarthritic patients and elucidated molecular mechanism of NF-kappaB-mediated Lef1 gene regulation in chondrocytes. Treatment of IL-1beta augmented Lef1 upregulation and nuclear translocation of NF-kappaB in chondrocytes. Under IL-1beta signaling, treatment of NF-kappaB nuclear translocation inhibitor SN-50 reduced Lef1 expression. A conserved NF-kappaB-binding site between mouse and human was selected through bioinformatic analysis and mapped at the 14 kb upstream of Lef1 transcription initiation site. NF-kappaB binding to the site was confirmed by chromatin immunoprecipitation assay. Lef1 expression was synergistically upregulated by interactions of NF-kappaB with Lef1/beta-catenin in chondrocytes. Our results suggest a pivotal role of NF-kappaB in Lef1 expression in arthritic chondrocytes or cartilage degeneration.
Yun
Kangsun
K
Department of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Choi
Yoo Duk
YD
Nam
Jong Hee
JH
Park
Zeeyoung
Z
Im
Sin-Hyeog
SH
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D053583:Interleukin-1beta; D051821:Lymphoid Enhancer-Binding Factor 1; D016328:NF-kappa B; D012333:RNA, Messenger; D051176:beta Catenin