Bone Abstracts

Arrest defective 1 was originally identified as an acetyltransferase essential for the life-cycle progression in yeasts. Its human orthologue hARD1 has been known to express the enzymatic activity and to acetylate several targets such as HIF-1alpha, MLCK-1, and beta-catenin. Here, whether hARD1 takes part in pre-osteoblast differentiation toward calcium-deposing osteoblast was explored. ALP staining and alizalin red S staining showed that osteoblast differentiation was negatively regulated by hARD1. Using two reporter systems reflecting the transcriptional activity of a runt-related transcription factor, hARD1 was suggested to control osteoblast differentiation by inhibiting the runt-related transcription factor. An immunoprecipitation analyses revealed that of runt-related transcription factors. Runx2 is physically interacted with and acetylated by hARD1. These results support the negative action of hARD1 against the Runx2-mediated osteoblast differentiation. Therefore, it was theoretically expected that hARD1 may be down-regulated during the differentiation because Runx2 should be activated to keep the differentiation. Ironically, the hARD1 expression was noticeably increased while osteoblasts undergo differentiation. Although the precise role of the hARD1-Runx2 interplay in bone formation is not uncovered so far, it could be speculated that hARD1 prevent the overshooting of Runx2 to ensure the harmonious cooperation among numerous osteogenic factors.