The utilization of bioresorbable synthetic bone substitutes with immunomodulatory properties has gained significant attention in dental clinical applications for the absorption of alveolar bone induced by orthodontic treatment. In this study, we developed two distinct materials: a conventional hydroxyapatite (HA) bone powder comprised of hydroxyapatite particles and nanoHA embedded within a poly(caprolactone-co-lactide) (PCLLA) elastomeric matrix. We assessed the physicochemical characteristics of the bone substitute, specifically focusing on its composition and the controlled release of ions. Our findings show that PCLLA-nanoHA has deformable properties under 40 N, and a significant release of Ca and P elements was noted after 7 days in aqueous settings. Moreover, at the protein and gene expression levels, PCLLA-nanoHA enhances the capacity of macrophages to polarize towards an M2 phenotype in vitro. In vivo, PCLLA-nanoHA exhibits comparable effects to standard HA bone powder in terms of promoting alveolar bone regeneration. Extensive investigations reveal that PCLLA-nanoHA surpasses the commonly employed HA bone powder in stimulating bone tissue repair in diabetic mice. We have identified that PCLLA-nanoHA regulates macrophage M2 polarization by activating the PI3K/AKT and peroxisome proliferator-activated receptor gamma (PPAR) signaling pathways, thereby facilitating a favorable local immune microenvironment conducive to bone repair and regeneration. Our findings suggest that PCLLA-nanoHA presents itself as a promising bioresorbable bone substitute with properties that promote macrophage M2 polarization, particularly in the context of regulating the local microenvironment of alveolar bone in diabetic mice, potentially facilitating bone tissue regeneration.

Background: Iron metabolism has emerged as a critical factor in cancer biology, with elevated intracellular iron levels contributing to increased oxidative stress and tumorigenesis. However, the molecular determinants governing ferroptosis sensitivity remain incompletely understood. Triosephosphate isomerase 1 (TPI1), a key glycolytic enzyme, has been implicated in cancer progression, but its role in ferroptosis regulation, particularly in the context of chemoresistance, is largely unexplored. In this study, we investigated the impact of TPI1 silencing on ferroptosis in cisplatin-resistant oral squamous cell carcinoma (OSCC), aiming to elucidate its mechanistic role and therapeutic potential. Methods: We conducted in vitro and in vivo analyses to evaluate the functional consequences of TPI1 knockdown in cisplatin-resistant OSCC cell lines and tumor xenograft models. The effects of TPI1 silencing and/or cisplatin treatment were assessed with respect to cell proliferation, migration, and invasion, along with ferroptosis-associated markers, including lipid ROS, free iron levels, lipid peroxidation, and the expression of key ferroptosis-related genes. Additionally, we analyzed the clinical relevance of TPI1 expression in human OSCC tissue samples, examining its association with clinicopathological features and patient prognosis. Results: TPI1 was found to be significantly upregulated in both OSCC tissues and cell lines, and high TPI1 expression correlated with poor clinical outcomes. Multivariate analysis identified TPI1 as an independent prognostic factor for tumor progression. Functionally, TPI1 knockdown suppressed OSCC cell proliferation, migration, and invasion, while its overexpression enhanced these oncogenic behaviors. Mechanistically, silencing TPI1 led to increased intracellular ROS accumulation, elevated free iron, and enhanced lipid peroxidation, collectively promoting ferroptotic cell death in cisplatin-resistant OSCC cells. In vivo, TPI1 depletion resulted in marked tumor growth inhibition and synergized with cisplatin to further suppress tumor burden in xenograft models. Moreover, TPI1 silencing disrupted the epithelial–mesenchymal transition (EMT), a key driver of cancer metastasis and drug resistance. Conclusions: Our study reveals a previously unrecognized role of TPI1 in protecting oral cancer cells from ferroptosis, especially in the setting of cisplatin resistance. These findings suggest that TPI1 not only contributes to tumor aggressiveness but also mediates resistance to ferroptosis. Targeting TPI1 may therefore represent a promising therapeutic strategy to overcome chemoresistance and enhance ferroptosis-based therapies in oral cancer.

Primary failure of eruption (PFE) is a rare oral disease with an incidence rate of 0.06%. It is characterized by abnormal eruption mechanisms that disrupt tooth eruption. The underlying pathogenic genetic variant and mechanism of PFE remain largely unknown. The purpose of this study was to explore the role of a novel transmembrane protein 119 (TMEM119) mutation in two PFE patients in a Chinese family. Information collection was performed on the family with a diagnosis of PFE, and blood samples from patients and healthy family members were extracted. Whole-exome sequencing was performed. Bioinformatics analysis revealed that a heterozygous variant in the TMEM119 gene (c.G143A, p.S48L) was a disease-associated mutation in this family. Recombinant pcDNA3.1 plasmid-containing wild-type and mutant TMEM119 expression cassettes were successfully constructed and transfected into MC3T3-E1 cells, respectively. The results of in vitro analysis suggested that the subcellular distribution of the TMEM119 protein was transferred from the cell cytoplasm to the nucleus, and the ability of cells to proliferate and migrate as well as glycolytic and mineralized capacities were reduced after mutation. Furthermore, rescue assays showed that activating transcription factor 4 (ATF4) overexpression rescued the attenuated glycolysis and mineralization ability of cells. Results of in vivo analysis demonstrated that TMEM119 was mainly expressed in the alveolar bone around the mouse molar germs, and the expression level increased with tooth eruption, demonstrated using immunohistochemistry and immunofluorescence. Collectively, the novel TMEM119 mutation is potentially pathogenic in the PFE family by affecting the glucose metabolism and mineralized function of osteoblasts, including interaction with ATF4. Our findings broaden the gene mutation spectrum of PFE and further elucidate the pathogenic mechanism of PFE.

Purpose: Research on primary maxillary central incisors (PMCIs) remains limited, and their morphological variations have rarely been documented. This study aimed to reconstruct anatomy of PMCIs in children from Beijing (China) and to analyse their commonalities and variations. Methods: Employing a threshold-based semi-automated region segmentation method, anatomical models of 101 PMCIs were reconstructed from existing cone-beam computed tomography (CBCT) images. Models were classified according to the Vertucci classification. For each variant type, representative morphological parameters of the hard tissue, pulp chamber, and canals were measured. The type with the highest prevalence was selected as the main type and its average model was constructed, representing the most common characteristics of PMCIs. Results: All PMCIs had a single root, whereas novel canal variations were identified. The most common canal type was Type I (61.4%), followed by Type V (20.8%) and Type III (17.8%). Anatomical parameters of main-type PMCIs were as follows: hard-tissue length = 15.76 ± 0.89 mm; pulp chamber and canal length = 12.94 ± 1.15 mm; and apical labial curvature angle was 22.57°. Statistical analysis indicated no differences between left and right, and no sex-related differences (p > 0.05). Statistically significant differences between the main-type and other variants were noted for several pulp-chamber and canal measurements (p < 0.05), but not for hard-tissue measurements (p > 0.05). An average main-type model was constructed; its inner and outer profiles conformed to the general characteristics of main-type PMCIs. Conclusion: PMCI canal variations were more complex than previously recognised, with uniform hard-tissue anatomy. Furthermore, an average main-type model was constructed, as a potentially valuable tool for dental education.