The role of the cartilage guanylyl cyclase-B receptor in craniofacial skeletal development

Objective C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is a potent endochondral bone growth factor that exerts its biological effects via the guanylate cyclase B (GC-B) receptor. We previously demonstrated that CNP knockout (KO) mice exhibited midfacial hypoplasia along the sagittal plane; however, the effects of GC-B (the receptor for CNP) on endochondral ossification in the maxillofacial region remain unclear, and the mechanism of the CNP/GC-B system has not been elucidated. Methods We investigated the physiological significance of GC-B in the cartilage of the craniofacial region through analysis of cartilage-specific GC-B KO mice. Morphological assessments were performed at 12 weeks old, with histological analyses performed at 2 weeks old. Results GC-B-KO mice exhibited sagittal midfacial hypoplasia, foramen magnum stenosis, and spinal canal stenosis. Histological examination revealed reduced thickness in the spheno-occipital synchondrosis (SOS), a critical growth center in cranio-maxillofacial skeletal development. The hypertrophic zone of the SOS exhibited reduced thickness, accompanied by a reduction in cell count in this area. Conclusions This study highlights the essential role of GC-B receptors in craniofacial morphology contributing to our understanding of the mechanisms underlying facial morphological abnormalities, foramen magnum stenosis, and spinal canal stenosis.