RRC ID 18605
著者 Kawato Y, Hirao M, Ebina K, Tamai N, Shi K, Hashimoto J, Yoshikawa H, Myoui A.
タイトル Nkx3.2-induced suppression of Runx2 is a crucial mediator of hypoxia-dependent maintenance of chondrocyte phenotypes.
ジャーナル Biochem Biophys Res Commun
Abstract Hypoxia is a key factor in the maintenance of chondrocyte identity. However, crucial chondrogenic transcription factors in the Sox families are not activated in this phenomenon, indicating that other pathways are involved. Nkx3.2 is a well-known chondrogenic transcription factor induced by Sonic hedgehog (Shh); it suppresses a key osteogenic transcriptional factor, Runt-related transcription factor 2 (Runx2), to maintain the chondrogenic phenotype in mesenchymal lineages. The purpose of this study was to examine the function of Nkx3.2 in hypoxia-dependent maintenance of chondrocyte identity. C3H10T1/2 pluripotent mesenchymal cells were cultured with rh-BMP2 (300 ng/ml) to induce chondrogenesis under normoxic (20% O(2)) or hypoxic (5% O(2)) conditions. Immunohistological detection of Nkx3.2 in a micromass cell culture system revealed that hypoxia promoted expression of the Nkx3.2 protein. Real-time RT-PCR analysis revealed that hypoxia promoted Nkx3.2 mRNA expression and suppressed Runx2 mRNA expression; however, Sox9 mRNA expression was not altered by oxygen conditions, as previously described. Over-expression of exogenous Nkx3.2 promoted glycosaminoglycan (GAG) production and inhibited Runx2 mRNA expression and, based on a dual luciferase assay, Runx2 promoter activity. Interestingly, downregulation of Nkx3.2 using RNAi abolished hypoxia-dependent GAG production and restored Runx2 mRNA expression and promoter activity. These results demonstrated that Nkx3.2-dependent suppression of Runx2 was a crucial factor in hypoxia-dependent maintenance of chondrocyte identity.
巻・号 416(1-2)
ページ 205-10
公開日 2011-12-9
DOI 10.1016/j.bbrc.2011.11.026
PII S0006-291X(11)02025-0
PMID 22093831
MeSH Anaerobiosis Animals Cell Line Chondrocytes / metabolism Chondrocytes / physiology* Chondrogenesis / genetics* Core Binding Factor Alpha 1 Subunit / genetics* Down-Regulation Gene Expression Regulation, Developmental* Genes, Reporter Homeodomain Proteins / biosynthesis* Homeodomain Proteins / genetics Mice Oxygen / metabolism* RNA, Messenger / biosynthesis RNA, Messenger / genetics Transcription Factors / biosynthesis* Transcription Factors / genetics Up-Regulation
IF 2.985
引用数 14
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 10T1/2(RCB0247)