en Molecular & Cellular Immunology Molecular & Cellular Immunology Review Review <p><span style="font-size:12px;"><span style="font-family:Tahoma;"><span style="line-height:107%"><span style="background:white"><span style="line-height:107%">Orthodontic tooth movement (OTM) is a complex biological process involving the precise remodeling of alveolar bone in response to mechanical forces. This remodeling is mediated by the coordinated activities of osteoblasts (responsible for bone formation) and osteoclasts (responsible for bone resorption) within the periodontal ligament (PDL). Mechanical stimuli are transduced into biochemical signals, which regulate cellular behavior through key signaling pathways such as RANKL/RANK/OPG and Wnt/&beta;-catenin.</span></span></span><br> <span style="line-height:107%"><span style="background:white"><span style="line-height:107%">MicroRNAs (miRNAs), as crucial post-transcriptional regulators of gene expression, play significant roles in skeletal development and bone homeostasis. They influence essential signaling cascades that govern the differentiation, function, and survival of osteoblasts and osteoclasts. Among them, miR-214 and miR-206 have emerged as potent negative regulators of osteoblast differentiation. This review focuses on how their common target, EphrinA2, plays a pivotal role in bone remodeling. EphrinA2 is a membrane-bound ligand critical for osteoclast-osteoblast communication. Upon binding to its receptor EphA2 on osteoblasts, EphrinA2 promotes osteoblast differentiation and bone formation. Dysregulation of the miR-214/miR-206&ndash;EphrinA2 axis impairs osteoblast function, disrupts bone remodeling, and can adversely affect the rate and stability of OTM.</span></span></span><br> <span style="background:white"><span style="line-height:107%">In conclusion, elucidating the regulatory functions of miR-214 and miR-206 and their modulation of EphrinA2 provides valuable insights into bone remodeling dynamics during OTM. Targeted manipulation of this pathway holds promise for developing novel molecular therapies that aim to enhance the efficacy, speed, and long-term stability of orthodontic treatments, while also addressing broader skeletal pathologies associated with disrupted bone remodeling</span></span></span></span></p> miR-214, miR-206, EphrinA2, osteoblast, orthodontic tooth movement, bone remodeling, microRNA 1110 1128 http://ijmcmed.org/browse.php?a_code=A-10-8469-1&slc_lang=en&sid=1 Hossein Salehivaziri vaziri1994@yahoo.com 100319475328460036827 100319475328460036827 No Department of Periodontology, School of Dentistry, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran Amir ali didar Dramiralididar2022@gmail.com 100319475328460036828 0009-0006-5604-7846 No Department of Endodontics, School of Dentistry, Ahvaz Jondishapoor University of Medical sciences, Ahvaz, Iran Maryam Sobhani dr.maryamsobhani1996@gmail.com 100319475328460036829 0009-0006-7244-5414 No Department of Orthodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran Ali Narimani Dr_ali_narimani@yahoo.com 100319475328460036830 0009-0000-3751-2913 No Department of Prosthodontics, Faculty of Dentistry, University of Medical Sciences, Tabriz, Iran Moslem Karimzadeh moslem.k90@gmail.com 100319475328460036831 0009-0008-6727-1916 Yes Islamic Azad University Tehran Medical Sciences, Tehran, Iran. Yasaman Bathaei y-bathaei@razi.tums.ac.ir 100319475328460036832 0009-0003-2649-4475 No Department of Orthodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran