title: Tauroursodeoxycholic acid suppresses endoplasmic reticulum stress in the chondrocytes of patients with osteoarthritis.
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.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Orthopedics, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Shan
authors.affiliation: Department of Orthopedics, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053454:Caspase 12 / Q000096:biosynthesis; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C506444:CASP12 protein, human; D053454:Caspase 12