Journal
DEVELOPMENT
Volume 143, Issue 12, Pages 2066-2076Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.131292
Keywords
Bone regeneration; Zebrafish; Jaw; Chondrocyte; Osteoblast; Ihha; Chondroid bone
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Funding
- California Institute for Regenerative Medicine (CIRM) New Investigator Award
- National Institutes of Health [R21 DE023899, R21 AR064462]
- University of Southern California Regenerative Medicine Initiative Award
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The healing of bone often involves a cartilage intermediate, yet how such cartilage is induced and utilized during repair is not fully understood. By studying a model of large-scale bone regeneration in the lower jawof adult zebrafish, we show that chondrocytes are crucial for generating thick bone during repair. During jawbone regeneration, we find that chondrocytes co-express genes associated with osteoblast differentiation and produce extensive mineralization, which is in marked contrast to the behavior of chondrocytes during facial skeletal development. We also identify the likely source of repair chondrocytes as a population of Runx2(+)/Sp7(-) cells that emanate from the periosteum, a tissue that normally contributes only osteoblasts during homeostasis. Analysis of Indian hedgehog homolog a (ihha) mutants shows that the ability of periosteal cells to generate cartilage in response to injury depends on a repair-specific role of Ihha in the induction as opposed to the proliferation of chondrocytes. The large-scale regeneration of the zebrafish jawbone thus employs a cartilage differentiation program distinct from that seen during development, with the bone-forming potential of repair chondrocytes potentially due to their derivation from osteogenic cells in the periosteum.
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