SGTB Promotes the Caspase-Dependent Apoptosis in Chondrocytes of Osteoarthritis

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• 作者：Guofeng Bao ; Libin Xu ; Xinbao Xu ; Leilei Zhai ; Chengwei Duan ; Dawei Xu…
• 刊名：Inflammation
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：39
• 期：2
• 页码：601-610
• 全文大小：583 KB
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• 作者单位：Guofeng Bao (1) (2)
  Libin Xu (3)
  Xinbao Xu (3)
  Leilei Zhai (3)
  Chengwei Duan (3)
  Dawei Xu (2)
  Jie Song (2)
  Zhongbing Liu (3)
  Ran Tao (3)
  Zhiming Cui (2)
  Huilin Yang (1)
  
  1. Department of Orthopedic Surgery, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China
  2. Department of Spine Surgery, the Second Affiliated Hospital of Nantong University, Nantong, 226001, China
  3. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Rheumatology
  Internal Medicine
  Pharmacology and Toxicology
  Pathology
  
• 出版者：Springer Netherlands
• ISSN：1573-2576

文摘

The purpose of this study is to investigate the expression of small glutamine-rich tetratricopeptide repeat (TPR)-containing β (SGTB) in articular cartilage of osteoarthritis (OA) and analyze the relationship between SGTB and chondrocyte apoptosis. We established an OA rat model by the meniscal/ligamentous injury (MLI) modeling method and observed the expression of SGTB in articular cartilage by immunohistochemistry and RT-PCR. Human SW1353 chondrosarcoma cells were treated with interleukin-1β (IL-1β) to mimic the OA-like chondrocyte injury in vitro, and Western blot was employed to examine the IL-1β-induced expression of SGTB and active caspase-3. The co-localization of SGTB and active caspase-3 was confirmed by immunofluorescence. We knocked down SGTB expression by RNA interference (RNAi) and overexpressed SGTB by plasmid transfection. Western blot was carried out to detect the knockdown/overexpressing efficiency of SGTB and evaluate its effects on IL-1β-stimulated expression of active caspase-3 in SW1353 cells. Annexin V/propidium iodide staining was used to detect chondrocyte apoptosis. Then, Western blot was carried out to examine the IL-1β-induced expression of Hsp70 and evaluate SGTB effects on IL-1β-stimulated expression of Hsp70 in SW1353 cells. SGTB expression was significantly up-regulated in articular cartilage of OA rat model. IL-1β stimulation increased the expression of SGTB and active caspase-3 in SW1353 cells. SGTB co-localized with active caspase-3 in IL-1β-treated SW1353 cells. SGTB inhibition significantly reduced IL-1β-stimulated expression of active caspase-3 in SW1353 cells. In line with this, overexpressing SGTB via Myc-SGTB transfection increased the active caspase-3 level in IL-1β-stimulated SW1353 cells. Moreover, flow cytometry assay demonstrated that SGTB knockdown alleviated IL-1β-induced apoptosis, but it was increased in SW1353 cells that overexpressed SGTB. Overexpressing SGTB via Myc-SGTB transfection decreased the Hsp70 level in IL-1β-stimulated SW1353 cells. Our results suggested that SGTB positively regulate the activation of caspase-3 by negatively regulating the activity of Hsp70 and might promote chondrocyte apoptosis in OA. This study may provide a novel insight into the pathophysiology of OA and a potential therapeutic target for its treatment.