How A Molecular Switch For Bone Formation Works

The transcriptional regulator Sp7/osterix could be the key to unlock the blueprint of bone formation in vertebrates, according to a genome-wide study.

AsianScientist (May 20, 2016) – A collaborative research group from Japan and the US has identified gene targets regulated by Sp7/osterix, a transcriptional regulator necessary for bone formation.

This finding, published in Developmental Cell, will contribute to the understanding of diseases of the skeleton and genome-based drug discovery for treatments and skeletal regeneration.

Bone is formed by cells called osteoblasts. Bone formation requires the normal function of Sp7/osterix, a member of a group of proteins called the Sp transcription family that acts as a switch to regulate the expression of osteoblast-related genes. Although the mechanisms underlying Sp7/osterix-mediated transcriptional regulation have been uncovered at a certain part of the genome, its genome-wide regulation remained unclear.

In this study, the research group of Project Associate Professor Shinsuke Ohba from the University of Tokyo Graduate School of Engineering and postdoctoral research associate Dr. Hironori Hojo from the University of Southern California identified a new mode of Sp7/osterix action.

It was thought that Sp7/osterix regulated gene transcription by binding directly to a specific part of the genome called GC box. However, the group discovered that Sp7/osterix regulates the transcription of osteoblast-related genes by indirectly binding to the genome via another protein called the homeobox transcription factor Dlx.

In addition, evolutionary analyses across different species suggest that the emergence of Sp7/osterix, whose modes of action are distinct from those of other Sp family members, are closely coupled to the emergence of bone-forming osteoblasts in the evolution of vertebrates.

“This finding is a milestone in our research goal of drawing a blueprint of bone formation based on genomic information and utilizing it to cure bone diseases,” said Ohba and Hojo.

The article can be found at: Hojo et al. (2016) Sp7/Osterix is Restricted to Bone-Forming Vertebrates where It Acts as a Dlx Co-factor in Osteoblast Specification.


Source: University of Tokyo; Photo: Shutterstock.
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