Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration.
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 jaw of 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.
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Sandeep
S
Paul
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Simone
S
Schindler
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Dion
D
Giovannone
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Alexandra
A
de Millo Terrazzani
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Francesca V
FV
Mariani
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA gcrump@usc.edu.
J Gage
0000-0002-3209-0026
JG
Crump
D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001861:Bone Regeneration; D002113:Calcification, Physiologic / Q000235:genetics; D002356:Cartilage / Q000166:cytology*; D019070:Cell Lineage; D019902:Chondrocytes / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000196:embryology; D053823:Hedgehog Proteins / Q000378:metabolism*; D007568:Jaw / Q000196:embryology / Q000502:physiology*; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology*; D010521:Periosteum / Q000166:cytology; D014945:Wound Healing; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism*
D015415:Biomarkers; D053823:Hedgehog Proteins; C569497:Ihha protein, zebrafish; D029961:Zebrafish Proteins
Bone regeneration; Chondrocyte; Chondroid bone; Ihha; Jaw; Osteoblast; Zebrafish