Regeneration of Bone, Cartilage, and Tooth Following Lower Jaw Amputation in Newts

Background/Objectives: In humans, diseases such as oral cancer may require surgical amputation of the jaw. This severe disruption causes impairments in eating, swallowing, and speech, leading to a significant decline in quality of life. In contrast, newts, a group of urodele amphibians, can regenerate their jaws even in adulthood. This study explored how adult newts reconstruct lower jaws after substantial loss and clarified how this process contributes to rapid functional recovery when feeding becomes impossible. Methods: Adult Japanese fire-bellied newts (Cynops pyrrhogaster) underwent surgical amputation of the anterior half of their lower jaws. Regeneration was monitored for 64 weeks using histological analyses of bone, cartilage, and dental tissues and micro-computed tomography (micro-CT)-based osteomorphometry to quantify structural changes in the regenerating lower jaw. Results: Histological observations and osteomorphometry revealed the following: epithelial coverage of the amputation margin; ectopic cartilage formation, growth, and regression; bone resorption at the amputation margin prior to bone regeneration; anterior extension of the lower jaw bone along the original dentition position, followed by its thickening; and dental lamina invagination with tooth germ formation. Through these processes, the lower jaw bone, Meckel's cartilage, and dentition were restored by 64 weeks post-amputation to their pre-amputation states. Conclusions: This study delineates the full sequence of lower jaw regeneration in adult newts, demonstrating complete restoration of bone, cartilage, and teeth after substantial lower jaw loss. These findings provide a detailed framework for understanding urodele jaw regeneration and may inform future strategies for promoting jaw reconstruction in humans.