Contribution of Chondrocyte-Derived C-Type Natriuretic Peptide to Craniofacial Growth

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C-type natriuretic peptide (CNP) serves as a key regulator of endochondral ossification. CNP promotes midfacial growth along the sagittal plane, and guanylate cyclase B (GC-B) (CNP receptor) is important for craniofacial skeletal development. However, the mechanism of the CNP/GC-B system underlying the regulation of endochondral ossification of the craniofacial region remains unclear. To clarify the contribution of chondrocyte-derived CNPto craniofacial region, we used cartilage-specific CNP knockout (KO) mice. The impact of CNP deficiency on craniofacial development was assessed through a two-tiered analysis. The mice underwent a morphological assessment at 12 weeks of age, followed by a histological assessment at 2 weeks of age. Cartilage-specific CNP KO mice showed reduced growth of the midfacial skeleton along the sagittal direction, as well as stenosis of both the foramen magnum (FM) and spinal canal. Histological analysis revealed a significant reduction in the thickness of the spheno-occipital synchondrosis (SOS), a critical site for craniomaxillofacial skeletal formation. The cell size and number within the hypertrophic zone of the SOS appeared to be decreased. These results suggest impaired endochondral ossification. This research elucidated the mechanisms of the CNP/GC-B system underlying craniofacial growth by evaluating the impact of CNP produced by chondrocytes themselves, providing further insights in the field.