Bone cells known as osteoblasts were recently shown to have a role in controlling the biochemical reactions that generate energy via secretion of the molecule osteocalcin. Gerard Karsenty and colleagues, at Columbia University College of Physicians and Surgeons, New York, therefore hypothesized that osteoblasts express a regulatory gene(s) that controls this osteoblast function and then identified Atf4 as this regulatory gene in mice.
Several genetic experiments established that lack of Atf4 in osteoblasts was central to these abnormal characteristics of mice lacking Atf4 and further analysis indicated the underlying mechanism. Specifically, Atf4 directly increased expression of the Esp gene, which makes a protein that decreases the activity of osteocalcin. As Atf4 in osteoblasts was already known to regulate bone formation and mineralization, the authors conclude that Atf4 regulates many, but not all, osteoblast functions.
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- Karsenty et al. The transcription factor ATF4 regulates glucose metabolism in mice through its expression in osteoblasts. Journal of Clinical Investigation, 2009;