HIF-1α prevents cell death despite hypoxia (red) in a wild-type tibia.

Johnson/CSH

Randall Johnson (University of California, San Diego, CA) and colleagues have found that cells need a particular transcription factor to survive in the hypoxic interior of developing bones. The critical activity of hypoxia-inducible factor 1α (HIF-1α), they say, is probably its inductionof a glycolytic metabolism appropriate to a low oxygen environment. Without this metabolic alteration, the bone-building chondrocytes may well suffer a catastrophic drop in ATP levels that is sufficient to induce their death.

A complete knockout of HIF-1α is lethal in mice, so Schipani et al. used the CRE system to delete HIF-1α only in chondrocytes. The resulting animals had shorter limbs, defective skeletons, and massive cell death in the cartilaginous centers of their bones. In theory these changes could arise because there is no HIF-1α present to induce angiogenesis, but the...

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