Effects Of Chronic Sleep Deprivation On The Extracellular Signal-regulated Kinase Pathway In The Temporomandibular Joint Of Rats

Objective:The aim of this study was to 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).Methods:270male8-week-old Wistar rats were randomly divided into three groups (n=90per group):chronic sleep deprivation (CSD) group, the chronic sleep deprivation with U0126injection (U0126) group, and the control (CON) group. The three groups were equally divided into three subgroups (n=30each) according to the observation time points (7,14, and21days).Rats were subjected to CSD using the modified multiple platform method (MMPM). Open field test (OFT) was performed, and the serum levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) were tested to assess the mental status of rats. 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 matrix metalloproteinase-1(MMP-1), MMP-3, and MMP-13expression levels were detected by real-time quantitative polymerase chain reaction (PCR) and Western blotting.Results: The crossing scores and rearing scores of CSD group rats in the open field were larger than those of CON groups (p<0.05). Serum CORT and ACTH levels of the CSD group were significantly elevated compared with those of the CON group (P<0.05).Hematoxylin and eosin (HE) staining and scanning electron microscopy (SEM) showed pathological alterations in the TMJ following CSD. In the rats administered the selective ERK inhibitor U0126, decreased tissue destruction was observed.Compared with CON group, the p-ERK protein expression in CSD group was significantly activated (P<0.01) and the total ERK expression showed no change (P>0.05). The mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13were upregulated after CSD (P<0.05).In the U0126group, phospho-ERK activation was visibly blocked (P<0.01) and the total ERK expression showed no change (P>0.05). The MMP-1, MMP-3, and MMP-13mRNA and protein levels were lower than the corresponding levels in the CSD without U0126group.Conclusion:MMPM is an ideal model that induces the rats to CSD stress state. CSD causes pathological alterations in the TMJ condylar cartilages which may be the basis of temporomandibular disorders.CSD can cause TMJ pathological alterations by activating the ERK pathway and upregulating the MMP-1, MMP-3, and MMP-13mRNA and protein levels in the TMJ condylar cartilage of rats, while blockage of ERK pathway can alleviate the tissue destruction. All these indicate that ERK pathway plays a key role in TMJ pathological alterations caused by CSD.