title: Chaperonin containing T-complex polypeptide subunit eta is a potential marker of joint contracture: an experimental study in the rat.
abstract: Joint contracture is a fibroproliferative disorder that restricts joint mobility, resulting in tissue degeneration and deformity. However, the etiology of joint contracture is still unknown. Chaperonin containing T-complex polypeptide subunit eta (CCT-eta) is reported to increase in fibrotic diseases. The purpose of this study was to investigate whether CCT-eta is implicated in joint contracture and to determine the role of CCT-eta in the progression of joint contracture by analyzing a rat model. We immobilized the left knee joint of rat by internal fixation for 8 weeks. The non-immobilized right leg served as a control. The range of motion (ROM) of the knee was investigated. Fibroblasts were obtained from the posterior joint capsule of the joints. The outcome was followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, fibroblast migration assay, and collagen assay. The effect of CCT-eta on the functions of fibroblasts was observed by utilizing a short inhibitory RNA (siRNA) targeting CCT-eta. The ROM of the immobilized joints was significantly limited compared to the contralateral joints (p < 0.05). Fibroblasts derived from the contractive joints showed higher mRNA and protein expressions of CCT-eta in parallel with alpha-smooth muscle actin (α-SMA) compared to the cells from the contralateral knees (p < 0.05). siRNA-mediated downregulation of CCT-eta inhibited the expressions of both CCT-eta and α-SMA. Moreover, the reduction of CCT-eta also significantly decreased fibroblast functions such as cell mobility and collagen synthesis (all p < 0.05). Our findings indicate that CCT-eta appears to be a potential marker of joint contracture disease.
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, China.
authors.forename: Ronghan
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, China.
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Junqi
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Orthopedic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 510000, Guangzhou, China. dr_wangkun333@163.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D003286:Contracture / Q000235:genetics / Q000378:metabolism*; D017746:Joint Capsule / Q000378:metabolism* / Q000473:pathology; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051381:Rats
chemical_list: D015415:Biomarkers; D056404:Chaperonin Containing TCP-1
keywords: CCT-eta; Fibrosis formation; Immobilization; Joint capsule; Joint contracture