Tauroursodeoxycholic acid suppresses endoplasmic reticulum stress in the chondrocytes of patients with osteoarthritis

Liu,Chao; Cao,Yongping; Yang,Xin; Shan,Pengcheng; Liu,Heng

doi:10.3892/ijmm.2015.2295

Tauroursodeoxycholic acid suppresses endoplasmic reticulum stress in the chondrocytes of patients with osteoarthritis

Authors:
- Chao Liu
- Yongping Cao
- Xin Yang
- Pengcheng Shan
- Heng Liu
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Affiliations: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China, Department of Orthopedics, Peking University First Hospital, Beijing 100034, P.R. China
Published online on: July 29, 2015 https://doi.org/10.3892/ijmm.2015.2295
Pages: 1081-1087

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Abstract

The main pathogenic events in osteoarthritis (OA) include loss and abnormal remodeling of cartilage extracellular matrix. The present study aimed to evaluate the protective effect of tauroursodeoxycholic acid on chondrocyte apoptosis induced by endoplasmic reticulum (ER) stress. Articular cartilage tissues were collected from 18 patients who underwent total knee arthroplasty and were analyzed histologically. Subsequently, chondrocyte apoptosis was assessed by TUNEL. Quantitative polymerase chain reaction and western blot analysis were employed to evaluate gene and protein expression, respectively, of ER stress markers, including glucose‑regulated protein 78 (GRP78), growth arrest and DNA‑damage‑inducible gene 153 (GADD153) and caspase‑12 along with type II collagen. Chondrocytes obtained from osteoarthritis patients at different stages were cultured in three conditions including: No treatment (CON group), tunicamycin treatment to induce ER stress (ERS group) and tauroursodeoxycholic acid treatment after 4 h of tunicamycin (TDA group); and cell proliferation, apoptosis, function and ER stress level were assessed. Degradation of cartilage resulted in histological damage with more apoptotic cartilage cells observed. Of note, GRP78, GADD153 and caspase‑12 mRNA and protein expression increased gradually from grade I to III cartilage tissue, while type II collagen expression decreased. Tunicamycin induced ER stress, as shown by a high expression of ER stress markers, reduced cell proliferation, increased apoptosis and decreased synthesis of type II collagen. Notably, tauroursodeoxycholic acid treatment resulted in the improvement of tunicamycin‑induced ER stress. These results indicated that ER stress is highly involved in the tunicamycin‑induced apoptosis in chondrocytes, which can be prevented by tauroursodeoxycholic acid.

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