title: Autoimmune regulator, Aire, is a novel regulator of chondrocyte differentiation.
abstract: Chondrocyte differentiation is controlled by various regulators, such as Sox9 and Runx2, but the process is complex. To further understand the precise underlying molecular mechanisms of chondrocyte differentiation, we aimed to identify a novel regulatory factor of chondrocyte differentiation using gene expression profiles of micromass-cultured chondrocytes at different differentiation stages. From the results of microarray analysis, the autoimmune regulator, Aire, was identified as a novel regulator. Aire stable knockdown cells, and primary cultured chondrocytes obtained from Aire(-/-) mice, showed reduced mRNA expression levels of chondrocyte-related genes. Over-expression of Aire induced the early stages of chondrocyte differentiation by facilitating expression of Bmp2. A ChIP assay revealed that Aire was recruited on an Airebinding site (T box) in the Bmp2 promoter region in the early stages of chondrocyte differentiation and histone methylation was modified. These results suggest that Aire can facilitate early chondrocyte differentiation by expression of Bmp2 through altering the histone modification status of the promoter region of Bmp2. Taken together, Aire might play a role as an active regulator of chondrocyte differentiation, which leads to new insights into the regulatory mechanisms of chondrocyte differentiation.
authors.affiliation: Laboratory of Epigenetic Skeletal Diseases, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Si
authors.forename: Kazuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Igarashi
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D006657:Histones; D014157:Transcription Factors; D000096927:AIRE Protein; C525719:Bmp2 protein, mouse
keywords: Aire; BMP2; Chondrocyte differentiation; Histone modification