{"title":"\"The role of mitogen-activated protein kinase signaling pathway in bone formation during mid-palatal suture expansion\".","authors":"Xiaoyue Xiao, Shujuan Zou, Zhiai Hu, Jianwei Chen","doi":"10.1080/03008207.2025.2498509","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.8000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Connective Tissue Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03008207.2025.2498509","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology.
The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented.
The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including
Biochemistry
Cell and Molecular Biology
Immunology
Structural Biology
Biophysics
Biomechanics
Regenerative Medicine
The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.
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