Bone healing, for example fracture repair in humans, often involves a cartilage intermediate but how this tissue is induced and contributes to healing is unclear. Here, Gage Crump and co-workers show that regeneration of the zebrafish jawbone involves cells of a hybrid cartilage-bone nature (p. ). They first report that the lower jawbone of adult zebrafish regenerates via a cartilage intermediate. The analysis of cells within this injury-induced cartilage reveals that they express both chondrocyte- and osteoblast-associated genes and can undergo mineralization. This is in contrast to the situation observed in developmental chondrocytes of zebrafish, which do not express osteoblast genes and do not mineralize. The researchers further report that these repair chondrocytes likely arise from the periosteum – a tissue that usually gives rise to osteoblasts. Finally, they demonstrate that the induction of repair chondrocytes from the periosteum involves an unexpected role for Indian hedgehog signalling, which is normally involved in chondrocyte proliferation during development. Thus, while it has generally been assumed that regeneration involves the same processes that are employed during development, this study suggests that regeneration induces a unique cartilage differentiation and repair programme.
