Periodontal Ligament Reactions to Orthodontic Force: A Transcriptomic Study on Maxillary and Mandibular Human Premolars

ABSTRACT Aims Orthodontic force (OF) induces a variety of reactions in the periodontal ligament (PDL) that could potentially account for individual variability regarding orthodontic tooth movement (OTM). This study investigates the transcriptomic profile of human PDL tissue subjected to OF in vivo for 7 and 28 days, additionally comparing the differences between maxillary and mandibular PDL. Methods Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of three groups: control (CG) where no OF was applied, 7 days and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50–100 g OF. Total RNA was extracted from the PDL tissue and analyzed via RNA‐seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of < 0.05 and ≥ 1.5 respectively. Functional and Protein–Protein Interaction analysis were performed. Results After 7 days of OF, the reaction of PDL to OF is characterized by cell responses to stress, increased bone resorption, inflammation and immune response, and decreased bone formation. In contrast, after 28 days, bone regeneration is more prominent, and processes of bone homeostasis, immune response, and cell migration are present. The response of maxillary and mandibular PDL was different. Bone resorption was observed in the maxilla at 7 and 28 days, while in the mandible expression of cell proliferation and transcriptional activity were predominant after 28 days of OF. Conclusions The early reaction of the PDL to OF corresponds with increased bone resorption and decreased bone formation. After 28 days, bone formation became more prominent. The maxillary and mandibular PDL present asynchronous responses during OTM. These findings enhance our comprehension of the mechanisms underlying the origin‐specific responses of PDL to different lengths of OF, which is potentially relevant in the development of personalized therapeutic strategies.