Molecular Changes Involving MEK3–p38 MAPK Activation in Chronic Masticatory Myalgia

• Published in: Journal of dental research Vol. 95; no. 10; pp. 1169 - 1175
• Main Authors: Meng, H., Gao, Y., Kang, Y.F., Zhao, Y.P., Yang, G.J., Wang, Y., Cao, Y., Gan, Y.H., Xie, Q.F.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.09.2016; SAGE PUBLICATIONS, INC
• Subjects: Adolescent; Adult; Aged; Blotting, Western; Calcium; Calcium channels (voltage-gated); Calcium Channels - genetics; Calcium Channels - metabolism; Chronic fatigue syndrome; Chronic illnesses; Chronic Pain - genetics; Chronic Pain - metabolism; Data analysis; Disease; DNA damage; DNA microarrays; Female; Fibromyalgia; Gene expression; Gene Expression Regulation, Enzymologic; Genomes; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Joint surgery; Kinases; Leukocytes; Male; MAP kinase; MAP Kinase Kinase 3 - genetics; MAP Kinase Kinase 3 - metabolism; Mastication; Medical research; Microarray Analysis; Middle Aged; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Myalgia; Myalgia - genetics; Myalgia - metabolism; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Pain; Pathogenesis; Peripheral blood; Phosphorylation; Polymerase chain reaction; Protein kinase; Proteins; Real-Time Polymerase Chain Reaction; Stomatognathic System - metabolism; Studies; Temporomandibular Joint Disorders - genetics; Temporomandibular Joint Disorders - metabolism; Up-Regulation; gene ontology; leukocytes; chronic pain; microarray analysis; CACNG2; temporomandibular disorders
• ISSN: 0022-0345; 1544-0591; 1544-0591
• DOI: 10.1177/0022034516659441

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.