Early proteomic signatures of impaired maxillary bone remodeling under mechanical stress in type 1 diabetes mellitus

Background: Type 1 diabetes mellitus (T1DM) compromises the mechanical adaptive capacity of bones, posing challenges in orthodontic treatment and increases periodontal complication risks. Mechanical loading is the main inducer of craniofacial bone adaptation; however, the early proteomic responses of the maxillary bone to stress under diabetic conditions remain unexplored. Therefore, we aimed to characterize the early proteomic signatures of the maxillary bone in T1DM rats subjected to controlled mechanical stress and identify potentially relevant molecular pathways for orthodontic treatment in patients with diabetes. Materials and methods: Sixteen male Wistar rats were randomly assigned to four groups: normoglycemic, normoglycemic + mechanical stress, diabetic, and diabetic + mechanical stress. T1DM was induced using streptozotocin, and mechanical loading was applied using a nickel-titanium expansion device for 4 days. Maxillary bone proteins were extracted, separated using two-dimensional gel electrophoresis, and identified using LC-MS. STRING-based protein interaction analysis was also conducted. Results: Nineteen differentially expressed protein spots were identified. STRING analysis revealed significant PPI enrichment and three interconnected functional clusters: cytoskeletal organization proteins (actin, cytoplasmic 2, and tropomyosin β chain), translation/proteostasis (eEF1A1 and apoptosis/β-catenin modulator 14-3-3 ζ/δ), and inflammatory/oxidative stress mediators (S100-A9, galectin-1, and HSPA8). Conclusions: Early T1DM-induced proteomic changes and mechanical stress impair the maxillary bone profile by reshaping cytoskeletal remodeling, translational regulation, and stress-response pathways during early mechanoadaptation. These findings provide a proteomic framework for understanding how metabolic dysregulation may influence craniofacial bone responses under orthodontic forces.