Details

Autor(en) / Beteiligte

• Li, Huang
• Zhang, Xiang-Yu
• Wu, Tuo-Jiang
• Cheng, Wei
• Liu, Xin
• Jiang, Ting-Ting
• Wen, Juan
• Li, Jie
• Ma, Qiao-Ling
• Hua, Zi-Chun

Titel

Endoplasmic Reticulum Stress Regulates Rat Mandibular Cartilage Thinning under Compressive Mechanical Stress

Ist Teil von

• The Journal of biological chemistry, 2013-06, Vol.288 (25), p.18172-18183

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Ca2+ 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. The molecular mechanisms of mechanical stress-induced cartilage thinning remain largely unknown. Endoplasmic reticulum stress (ERS) was activated in chondrocytes during mechanical stress loading. ERS inhibition suppressed the apoptosis and restored the proliferation and cartilage thinning. ERS regulates mechanical stress-induced cartilage thinning. Our data demonstrate a novel pathological role for ERS and provide new insight into the treatment of temporomandibular joint diseases.