BMP regulates endochondral growth in the cranial base synchondroses

The molecular mechanisms that control endochondral growth in the cranial base synchondroses are not well known. However, there is evidence that members of the TGF-beta growth factor family play an important role in the regulation of craniofacial bone growth. However, the specific role that these factors play in cranial base synchondroses-mediated growth has not been well elucidated.

Objective: The goal of this study was to determine whether BMP2, a member of the TGF-beta growth factor family, modulates growth in the spheno-occipital synchondrosis. The study aimed at determining the effect of BMP2 deficiency on the spheno-occipital synchondrosis using a BMP2 conditional knockout mutant mouse model.

Methods: Three-week-old skulls from BMP2 conditional knockout mice and age matched wild type mice were examined by radiography and cephalometry. Spheno-occipital synchondroses from mutants and wild type mice were excised and processed for histology; including hematoxylin/eosin, and alcian blue staining, as well as immunohistochemistry.

Results: Radiography and cephalometry revealed calvarial bossing, decreased naso-occipital length, and midface retrognathia in the BMP2 conditional knockout mice. This was due to incomplete anterior growth of the maxilla. On histological analysis, the synchondroses of the BMP2 conditional knockout mice were significantly decreased in both width and length compared to the wild type.

Conclusions: The absence of BMP2 results in craniofacial anomalies associated with abnormal growth and morphology of the spheno-occipital synchondrosis. This indicates that BMP2 plays a key role in regulating growth in the cranial base synchondroses. Further understanding of the molecular mechanisms involved in BMP2-mediated effects may be useful for diagnosing and treating disorders associated with maxillary retrognathia.

Supported by UTHSCSA COSTAR program training grant NIDCR T-32 DE14318 and the AAOF Faculty Development Fellowship