Craniofacial Bone Density is Regulated by Thyroid Hormone in Zebrafish

Abstract

Thyroid hormone (TH) facilitates developmental transitions, particularly by modulating cell proliferation and differentiation. Its role in regulating skeletal growth is well documented. Previous work from our lab and others have demonstrated that hypo- and hyperthyroid fish display changes in bone shape, ossification and the timing of ossification5. Zebrafish (Danio rerio) develop bone quickly, grow indefinitely throughout their lives, are highly amenable for imaging, and are a valuable model for skeletal biology research. Using Danio rerio, we sought to study the long-term effects of TH on bone density by rearing and comparing normal euthyroid (Eu) with a transgenically thyroid-ablated hypothyroid (TH-) and mutant hyperthyroid (TH+) fish. We found that TH strongly affects bone density and volume. We further hypothesize that TH is critical for the timing and fidelity of skeletogenesis. In hormone-dysregulated fish, we found that massive bone and cartilage exostoses grow on the dentary. Thyroid hormone’s effects are highly bone-specific: in TH- fish, we see reduced density in many craniofacial bones, but also increased volume and mineralization in other regions of the dentary. These data suggest that TH plays a critical role in coordinating bone mineralization with growth.