Importance of Endochondral Ossification in Craniofacial Morphology

Objectives: Craniofacial skeletogenesis is known to be characterized by the growth of a number of bones via endochondral or membranous ossification. Nevertheless, the comprehensive effects of endochondral ossification on craniofacial skeletogenesis have not been fully elucidated. On the other hand, C-type natriuretic peptide (CNP), one of the members of the natriuretic peptide family, is known to be a strong promoting factors of endochondral ossification. In this study, we investigated the importance of endochondral ossification on craniofacial skeletogenesis, using cartilage-specific CNP knockout (C-CNP-KO) mice and cartilage-specific CNP transgenic (C-CNP-Tg) mice.
Methods: Craniofacial morphology of C-CNP-KO or C-CNP-Tg mice was analyzed using μCT images. Furthermore, using C-CNP-KO or C-CNP-Tg mice, we analyzed the craniofacial cartilage (spheno-occipital synchondrosis (SOS), nasal septal cartilage (NSC), and mandibular condylar cartilage (MCC)), which is believed to play an important role in craniofacial growth.
Results: The upper jaws of C-CNP-KO mice were longitudinally shorter, whereas those of C-CNP-Tg mice were longer in sagittal direction, compared with those of WT mice. Histological examination revealed that SOS was markedly narrower in C-CNP-KO skull bases and wider in C-CNP-Tg skull bases at the age of 2 weeks. In micromass culture experiment using NSC, the thickness of micromass from C-CNP-KO mice was thinner and that from C-CNP-Tg mice were thicker.
With respect to the mandible, lower jaws of C-CNP-KO mice revealed shorter than those of WT mice, and CNP stimulated endochondral bone growth of MCC in cultured fetal murine mandibles. But differences in the lengths of the lower jaw between C-CNP-KO or C-CNP-Tg mice and WT mice were smaller than those observed in the lengths of the upper jaw.
Conclusions: Craniofacial morphology is strongly influenced by endochondral ossification of craniofacial region. In particular, it is important for the midfacial growth in the sagittal direction.