title: Effects of chronic sleep deprivation on the extracellular signal-regulated kinase pathway in the temporomandibular joint of rats.
abstract: OBJECTIVE
  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
  Rats 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Stomatology, Jinan Military General Hospital, Jinan City, Shandong Province, China; College of Stomatology, Shandong University, Jinan City, Shandong Province, China; Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan City, Shandong Province, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Stomatology, Jinan Military General Hospital, Jinan City, Shandong Province, China.
authors.forename: Gaoyi
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Stomatology, Jinan Military General Hospital, Jinan City, Shandong Province, China.
authors.forename: Zhaoling
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Jinan Military General Hospital, Jinan City, Shandong Province, China.
authors.forename: Peihuan
authors.initials: P
authors.lastname: Wang
authors.affiliation: cardiovascular medicine, He Bei medical University, Shijiazhuang City, Hebei Province, China.
authors.forename: Longmei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Stomatology, Jinan Military General Hospital, Jinan City, Shandong Province, China.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Zhu
authors.affiliation: College of Stomatology, Shandong University, Jinan City, Shandong Province, China; Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan City, Shandong Province, China.
authors.forename: Huaqiang
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D012892:Sleep Deprivation / Q000235:genetics / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D000324:Adrenocorticotropic Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D003345:Corticosterone