"The role of mitogen-activated protein kinase signaling pathway in bone formation during mid-palatal suture expansion".

PURPOSE: Orthodontic interventions such as maxillary expansion are pivotal in correcting malocclusions; however, the intracellular mechanisms of bone remodeling during this process are not well understood. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in bone remodeling during maxillary expansion and relapse in rats. MATERIALS AND METHODS: Thirty male Wistar rats were randomly divided into three groups: Control (Ctrl), Expansion only (EO), and Expansion with MEK inhibitor U0126 (EO + INH). Customized expanders applied 100 g force for seven days, followed by natural relapse. Tissue changes within the mid-palatal suture were assessed via micro-computed tomography, histology, and immunohistochemistry. In vitro, primary bone marrow mesenchymal stem cells (BMSCs) were exposed to cyclic tensile stress with or without MAPK inhibition, followed by evaluation of protein expression, alkaline phosphatase activity, and Alizarin red staining. RESULTS: The EO group showed a significant increase in maxillary arch width compared to the EO + INH group, a difference that remained significant after relapse. This group also had higher levels of phosphorylated mitogen-extracellular kinase (p-MEK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated Ets-like transcription factor 1 (p-ELK1), along with increased osteoblast markers and bone resorption. Conversely, MAPK inhibition impeded bone remodeling, indicated by decreased osteogenic markers and fewer TRAP-positive cells. In vitro, tensile stress enhanced osteogenic differentiation, which was attenuated with MAPK inhibition. CONCLUSIONS: Mechanical activation of MEK-ERK1/2-ELK1 pathway is essential for effective maxillary expansion. Thus, inhibiting this pathway significantly impairs bone remodeling, underscoring its potential as a therapeutic target to enhance bone formation in orthodontic treatments.