Partial cementocyte ablation does not reduce cellular cementum apposition in a mouse model of molar super-eruption

Abstract

Cementocytes reside in the cellular cementum of the apical tooth root and resemble bone osteocytes in their markers, lacunocanalicular network, and response to mineralization defects. However, it is unclear if cementocytes have a role in regulating cellular cementum similar to that of osteocytes in controlling bone formation and resorption. The Dmp1Cre-iDTR^fl/fl (Dmp1-DTR) mouse sensitizes Dmp1-expressing cells, including osteocytes and cementocytes, to diphtheria toxin (DT), allowing selective ablation of cell populations. Compared to iDTR^fl/fl control (CTR) mice, 1.0 μg/kg intraperitoneal DT administration at 6 and 8 weeks of age increased femur cortical bone porosity and reduced alveolar bone density in Dmp1-DTR mice, validating the model. DT administration eliminated approximately 80 % of alveolar bone osteocytes and 60 % of cementocytes in Dmp1Cre-iDTR^fl/fl mice. Mice were subjected to the challenge of unopposed first molar super-eruption, which promotes increased cellular cementum apposition. Maxillary molars were bilaterally extracted at 7 weeks, and effects on cellular cementum accumulation in mandibular first molars were analyzed at 3 weeks post-procedure using micro-computed tomography and histology. DT-directed cementocyte ablation did not alter cellular cementum volume, density, or porosity vs. CTR mice. Immunostaining showed similar distributions between treatment groups of osteopontin (OPN), an extracellular matrix protein associated with axial tooth movement. Localization of DMP1 in cellular cementum and cementocyte networks of Dmp1-DTR mice appeared reduced compared to CTR mice. Within the limits of the study, these results suggest that cementocytes are not essential for new cellular cementum formation under challenge. Further insights into roles for cementocytes require additional in vivo approaches.