title: Endoplasmic reticulum stress regulates rat mandibular cartilage thinning under compressive mechanical stress.
abstract: Compressive mechanical stress-induced cartilage thinning has been characterized as a key step in the progression of temporomandibular joint diseases, such as osteoarthritis. However, the regulatory mechanisms underlying this loss have not been thoroughly studied. Here, we used an established animal model for loading compressive mechanical stress to induce cartilage thinning in vivo. The mechanically stressed mandibular chondrocytes were then isolated to screen potential candidates using a proteomics approach. A total of 28 proteins were identified that were directly or indirectly associated with endoplasmic reticulum stress, including protein disulfide-isomerase, calreticulin, translationally controlled tumor protein, and peptidyl-prolyl cis/trans-isomerase protein. The altered expression of these candidates was validated at both the mRNA and protein levels. The induction of endoplasmic reticulum stress by mechanical stress loading was confirmed by the activation of endoplasmic reticulum stress markers, the elevation of the cytoplasmic Ca(2+) level, and the expansion of endoplasmic reticulum membranes. More importantly, the use of a selective inhibitor to block endoplasmic reticulum stress in vivo reduced the apoptosis observed at the early stages of mechanical stress loading and inhibited the proliferation observed at the later stages of mechanical stress loading. Accordingly, the use of the inhibitor significantly restored cartilage thinning. Taken together, these results demonstrated that endoplasmic reticulum stress is significantly activated in mechanical stress-induced mandibular cartilage thinning and, more importantly, that endoplasmic reticulum stress inhibition alleviates this loss, suggesting a novel pharmaceutical strategy for the treatment of mechanical stress-induced temporomandibular joint diseases.
authors.affiliation: School of Stomatology and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 30 Zhongyang Road, Nanjing 210009, China. Lihuang76@nju.edu.cn
authors.forename: Huang
authors.initials: H
authors.lastname: Li
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhang
authors.forename: Tuo-Jiang
authors.initials: TJ
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jiang
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Ma
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D059865:Endoplasmic Reticulum Stress; D008297:Male; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013314:Stress, Mechanical
chemical_list: D020543:Proteome
keywords: Cartilage; Chondrocytes; ER Stress; Mechanotransduction; Proteomics