Sunday, July 18, 2010


Autoimmune regulator, Aire, is a novel regulator 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 Aire binding site (T box) in the Bmp2 promoter region in the early stages of chondrocyte differentiation and histone methylation was modified. 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."

Full-size image (84 K)
C lists other potential factors to look into for chondroinduction.  Aire was the only gene successfully validated in D.  Although Atoh8 and Erg could also be candidates.

"Aire−/− mice did not exhibit significant abnormal phenotypes in skeletal morphology. However, patients with mutations at the AIRE gene locus suffer from autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) and some of them show reversible metaphyseal dysplasia (RMD) with notable progressive growth and abnormal endochondral ossification in adolescents. Cst10−/− mice developed and grew normally but showed abnormal phenotypes in formation of osteoarthritic osteophytes, age-related ectopic ossification and healing of bone fractures"

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