title: Molecular Changes Involving MEK3-p38 MAPK Activation in Chronic Masticatory Myalgia.
abstract: The exact mechanism underlying chronic masticatory myalgia (CMM), a conspicuous symptom in temporomandibular disorders, remains unclear. This investigation compared gene expression profiles between CMM patients and healthy subjects. Peripheral blood leukocytes were collected in 8 cases and 8 controls and subjected to whole genome microarray analyses. Data were analyzed with Gene Ontology and interactive pathways analyses. According to Gene Ontology analysis, categories such as ion transport, response to stimuli, and metabolic process were upregulated. The pathway analysis suggested overexpression of the mitogen-activated protein kinase (MAPK) pathway in CMM patients and to a higher degree in a pathway network. Overexpression of representative members of the MAPK pathway-including MAPK kinase 3 (MEK3), calcium voltage-gated channel auxiliary subunit gamma 2 (CACNG2), and growth arrest and DNA damage-inducible gamma (GADD45G)-was validated with real-time polymerase chain reaction. The upregulation of MEK3 was negatively correlated with the age of the CMM group. In the next step, the authors focused on MEK3, the gene that exhibited the greatest degree of differential expression, and its downstream target protein p38 MAPK. The results revealed upregulation of MEK3, as well as phosphorylated MEK3 and phosphorylated p38 MAPK, in CMM patients. These results provide a "fingerprint" for mechanistic studies of CMM in the future and highlight the importance of MEK3-p38 MAPK activation in CMM.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China Department of Prosthodontics, North China University of Science and Technology School of Stomatology, Hebei, China.
authors.forename: H
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Kang
authors.affiliation: Center for TMD and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: G J
authors.initials: GJ
authors.lastname: Yang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Gan
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China Center for Oral Functional Diagnosis, Treatment, and Research, Peking University School and Hospital of Stomatology, Beijing, China xieqiuf@163.com.
authors.forename: Q F
authors.initials: QF
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D059350:Chronic Pain / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D048371:MAP Kinase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D063806:Myalgia / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D013284:Stomatognathic System / Q000378:metabolism*; D013705:Temporomandibular Joint Disorders / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D015220:Calcium Channels; D047908:Intracellular Signaling Peptides and Proteins; D048371:MAP Kinase Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C491912:CACNG2 protein, human; C485654:GADD45G protein, human; D000097642:GADD45 Proteins; C482530:MAP2K3 protein, human
keywords: CACNG2; chronic pain; gene ontology; leukocytes; microarray analysis; temporomandibular disorders