Novel Roles of Nestin in Postnatal Root Formation

<b>Background/Objectives:</b> Nestin is an intermediate filament protein and a marker of odontoblasts, but its function in tooth and bone formation is largely unknown. This study aimed to determine whether Nestin plays a role in postnatal tooth formation. <b>Methods:</b> 4-week-old Nestin knockout (KO) mice were analyzed with a range of techniques, including X-ray imaging, uCT, backscattered and acid-etched casted SEM, FITC-confocal microscopy, H&E and TRAP staining, and immunohistochemistry. <b>Results:</b> The KO mice had no apparent difference in crown formation compared to age-matched wild-type (WT) but showed delayed molar eruption with reduced TRAP⁺ osteoclasts. More importantly, KO mice developed expanded predentin and shorter, thinner roots with irregular and shortened dentin tubules. Additionally, the Nestin KO mice exhibited a reduced cellular cementum mass with sharp reductions in DMP1, OPN, and BSP. <b>Conclusions:</b> These findings suggest that Nestin plays a critical role in the postnatal development of root dentin and cellular cementum.