TMJ Development and Growth Require Primary Cilia Function

Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia...

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Bibliographic Details
Published in:Journal of dental research 2011-08, Vol.90 (8), p.988-994
Main Authors: Kinumatsu, T., Shibukawa, Y., Yasuda, T., Nagayama, M., Yamada, S., Serra, R., Pacifici, M., Koyama, E.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bone growth
Cartilage
Cartilage, Articular - metabolism
Cells, Cultured
Chondrocytes
Chondrocytes - cytology
Chondrogenesis - genetics
Cilia
Cilia - physiology
Collagen (type I)
Collagen Type I - genetics
Collagen Type I - metabolism
Dentistry
Embryology: invertebrates and vertebrates. Teratology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Developmental
Growth Plate - metabolism
Hedgehog protein
Hedgehog Proteins - genetics
Hedgehog Proteins - physiology
Intramembraneous bone
Kinesin - genetics
Kinesin - physiology
Mandibular Condyle - growth & development
Mice
Mice, Knockout
Mitosis
Organogenesis. Physiological fonctions
Ossification
Ossification, Heterotopic - genetics
Osteogenesis
Osteogenesis - genetics
Patched protein
Patched Receptors
Patched-1 Receptor
Perichondrium
Protein transport
Receptors, Cell Surface - genetics
Receptors, Cell Surface - physiology
Signal Transduction
Sox9 protein
SOX9 Transcription Factor - genetics
SOX9 Transcription Factor - physiology
Sp7 Transcription Factor
Temporomandibular joint
Temporomandibular Joint - growth & development
Transcription Factors - genetics
Transcription Factors - physiology
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Summary:Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction.
ISSN:0022-0345
1544-0591
DOI:10.1177/0022034511409407