Promotes Cementum and Alveolar Bone Growth in a Time-Dependent Manner.

The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a inducible transgenic mouse model targeting -expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro-computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of expression and a 3-fold increased bone volume after 9 wk of expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of expression. However, 9 wk of expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of expression revealed that expression affects mandibular bone and growing incisors but not molar teeth, indicating that influences only growing tissues. To further investigate the effect of on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing -HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry.