Effects of chronic sleep deprivation on the extracellular signal-regulated kinase pathway in the temporomandibular joint of rats.

Chuan Ma,Huaqiang Zhao,Guoxiong Zhu,Zhaoling Wang,Gaoyi Wu,Peihuan Wang,Longmei Wu,Zhuoli Zhang

doi:10.1371/journal.pone.0107544

Abstract

ObjectivesTo examine the possible involvement and regulatory mechanisms of extracellular signal-regulated kinase (ERK) pathway in the temporomandibular joint (TMJ) of rats subjected to chronic sleep deprivation (CSD).MethodsRats were subjected to CSD using the modified multiple platform method (MMPM). The serum levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) were tested and histomorphology and ultrastructure of the TMJ were observed. The ERK and phospho-ERK (p-ERK) expression levels were detected by Western blot analysis, and the MMP-1, MMP-3, and MMP-13 expression levels were detected by real-time quantitative polymerase chain reaction (PCR) and Western blotting.ResultsThe elevated serum CORT and ACTH levels confirmed that the rats were under CSD stress. Hematoxylin and eosin (HE) staining and scanning electron microscopy (SEM) showed pathological alterations in the TMJ following CSD; furthermore, the p-ERK was activated and the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13 were upregulated after CSD. In the rats administered with the selective ERK inhibitor U0126, decreased tissue destruction was observed. Phospho-ERK activation was visibly blocked and the MMP-1, MMP-3, and MMP-13 mRNA and protein levels were lower than the corresponding levels in the CSD without U0126 group.ConclusionThese findings indicate that CSD activates the ERK pathway and upregulates the MMP-1, MMP-3, and MMP-13 mRNA and protein levels in the TMJ of rats. Thus, CSD induces ERK pathway activation and causes pathological alterations in the TMJ. ERK may be associated with TMJ destruction by promoting the expression of MMPs.

Highlights

The temporomandibular joint (TMJ) is a specialized synovial joint essential for the function of the mammalian jaw, and it plays an important role in craniofacial growth and function
Increased concentration of serum CORT and adrenocorticotropic hormone (ACTH) To verify that the experimental rats were under chronic sleep deprivation (CSD) stress, we analyzed the serum CORT and ACTH levels
The serum ACTH concentrations after 7, 14, and 21 days of sleep deprivation were significantly higher in the CSD group than in the CON group

Summary

Introduction

The temporomandibular joint (TMJ) is a specialized synovial joint essential for the function of the mammalian jaw, and it plays an important role in craniofacial growth and function. Temporomandibular disorder (TMD) is a functional disorder of the TMJ and has been reported to affect an estimated 9%–15% of the adult population in North America [1]. Another study has reported that psychosocial factors are important in the etiology and maintenance of TMD [2]. Studies have consistently shown that the majority of patients with TMD report poor sleep quality and that the subjective ratings of poor sleep are associated with increased severity of clinical pain and psychological distress [4,5,6]. Many studies of sleep disturbance in TMD are epidemiological reports, clinical case studies, or questionnaire surveys [7,8]. Few well-controlled experiments have been carried out on sleep disorders in TMD because it is difficult to establish a research model of sleep disturbance on TMD and involves many factors that are complicated to index and quantify

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