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Fig. 7
Osteoblast dedifferentiation and migration represent generic injury responses that are differentially regulated and can occur independently of each other and of regenerative bone growth. Upper panel: After fin amputation, osteoblasts downregulate the expression of differentiation markers. The extent depends on their distance to the amputation site, with osteoblasts close to the amputation site displaying more pronounced dedifferentiation. In addition, osteoblasts elongate and migrate towards the amputation plane and beyond to found osteogenic cells in the blastema (pink). Thus, osteoblast dedifferentiation, migration, and bone regeneration are all distally oriented. Osteoblast dedifferentiation is negatively regulated by NF-κB and retinoic acid signalling, while actomyosin dynamics and the complement system are required for directed osteoblast migration. Lower panel: In the hemiray removal model, a proximal and a distal injury are created on both sides of a remaining centre segment. The extent of osteoblast dedifferentiation is even along the centre segment, and osteoblasts migrate towards both injury sites. Yet, only at the distally-facing site, osteoblasts migrate into the bone defect, and blastema formation and bone regeneration only occur here.