Title: Temporomandibular Joint Defects in Bmp7-Deficient Mice
Arleen Schmidt (Presenter)
University of Alberta
Pranidhi Baddam, University of Alberta
Daniel Graf, University of Alberta
Objectives: Loss of Bone Morphogenetic Protein 7 (BMP7), an osteogenic signaling molecule, in cranial neural crest cells leads to a variety of craniofacial developmental defects, such as high-arched palate, submucosal cleft, midfacial hypoplasia, retrognathia and nasal airway obstruction. As loss of Bmp7 in peripheral mesenchymal cells leads to early onset arthritis in mice, we investigated whether deletion of Bmp7 in neural crest cells would also lead to changes in temporomandibular joint (TMJ) that may be associated with development of arthritis.
Methods: Micro-computed tomography (μCT) datasets from 4- and 8-week old Bmp7 control and Bmp7fl:wnt1Cre (mutant) mice were analyzed for morphological changes to the mandible using AMIRA software. To understand and correlate morphological changes to histological differences, sagittal paraffin sections of the TMJ from 4-week old mice were investigated. To correlate changes to Bmp7 expression, Bmp7lacZ reporter mice were used.
Results: LacZ expression revealed that Bmp7 is expressed in the articular lining of the TMJ. μCT analysis indicated a smaller and more acutely angled condylar head in mutant mice. Histological analysis revealed changes to condylar cell composition including loss of cells in the articular layer with the articular cartilage potentially being replaced by bone; expansion of the proliferative and chondrogenic layers; but no obvious changes to the hypertrophic layer. These findings were corroborated by immunohistochemical assessment for expression of cartilage and bone markers Osteopontin and Osterix and pSmad1/5/8 as indicator of BMP signaling.
Conclusions: This data indicate that BMP7 is important for the normal physiology of the TMJ and condylar head structure. It might be expected that older mice will develop TMJ osteoarthritis and thus could serve as a model for this debilitating condition.