Zachary Yellen
Research Mentor: Yuji Mishina
Mentor Department: Biological and Material Sciences, Dentistry
Author(s): Zachary Yellen, Yuji Mishina
Session: Session 7 (4:00 PM – 4:50 PM)
Presentation Type: Poster 14
Abstract
The temporomandibular joint (TMJ) is a unique joint whose maintenance and development rely on secondary cartilage formed from the cranial neural crest. Bone Morphogenetic Protein (BMP) signaling has been shown to be a critical regulator of endochondral ossification, but its specific role in TMJ cartilage development remains poorly understood. This study uses a mutant mouse model to investigate how augmenting BMP signaling affects TMJ development and systemic growth. The mutant mice carry the constitutively activated Acvr1 (caA2) and Osterix-Cre genes to express caA2 and augment BMP signaling in all osteoblasts. Mutants appear to suffer from progressive growth hindrance, which was verified through morphometric analysis. The mutants exhibit significant morphometric divergence from the controls, especially around the weaning period, potentially suggesting that poor TMJ development prevents mutants from meeting their metabolic demands through chewing. For example, P14/15 mutants average 4.24 cm in length and 3.57 g in weight compared to 5.53 cm and 6.92 g in controls. Whole-mount skeletal staining using Alcian Blue and Alizarin Red revealed that mutant mice lack TMJ secondary cartilage present in controls (among other morphological differences). Future analyses of these samples will involve histology with H&E staining to create a timeline of the localized development/breakdown of the TMJ. Additionally, we will use immunohistochemistry to examine the extent of BMP augmentation, chondrogenesis regulation, and potential connection with Noggin (a BMP antagonist) involvement and the Fibroblast Growth Factor (FGF) pathway through looking at pSMAD1/5/9, SOX9, and FGFR2 involvement, respectively. Ultimately, this study provides an effective non-injury model for understanding temporomandibular disorders (TMD) and how TMD complications may extend beyond the TMJ to affect systemic growth. Understanding these relationships may inform future research using these mouse models and may inform more comprehensive clinical interventions for treating TMD in human patients.
