title: Regulation of a disintegrins and metalloproteinase with thrombospondin motifs 7 during inflammation in nucleus pulposus (NP) cells: role of AP-1, Sp1 and NF-κB signaling.
abstract: OBJECTIVE
  The objective of this study is to explore the effect of inflammatory cytokines on a disintegrins and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) and to demonstrate the role of Sp1, AP-1 and NF-κB signaling on the ADAMTS7 regulation during inflammation in NP cells.
  
  
  METHODS
  Real-time PCR was to detect the effect of ADAMTS7 knockdown on the expression of catabolic enzymes during inflammatory condition in NP cells. Real-time PCR, western blot, immunofluorescence and transfection experiments were used to observe the effect of tumor necrosis factor-α (TNF-α) or interleukin-1β on the expression and the activity of ADAMTS7, and demonstrated the role to Sp1, AP-1 and NF-κB in the regulation of ADAMTS7 during inflammation.
  
  
  RESULTS
  As other cells, ADAMTS7 knockdown suppressed the mRNA expression of catabolic factors during inflammation in human NP cells. However, the expression of ADAMTS7 mRNA and protein and the activity of ADAMTS7 promoter were refractory to inflammatory cytokines. In addition, Sp1, AP-1, not NF-κB signaling sustained the expression of ADAMTS7 mRNA, protein, as well as promoter activity during inflammation in NP cells.
  
  
  CONCLUSIONS
  ADAMTS7 played a crucial role in the expression of catabolic genes in the presence of TNF-α and AP-1, Sp1, not NF-κB signaling were critical for the maintenance of ADAMTS7 expression during inflammation in NP cells.
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Xiaofei
authors: X
authors: Wang
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China.
authors: Chunhai
authors: C
authors: Li
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China.
authors: Anjing
authors: A
authors: Liang
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China.
authors: Yan
authors: Y
authors: Peng
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Jianchao
authors: J
authors: Sun
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China.
authors: Dongsheng
authors: D
authors: Huang
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. xukang1995@yahoo.com.|Experimental Center of Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China. xukang1995@yahoo.com.
authors: Kang
authors: K
authors: Xu
authors: Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yan Jiang Xi RD 107, Guangzhou, 510120, China. yewei3@mail.sysu.edu.cn.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. yewei3@mail.sysu.edu.cn.
authors: Wei
authors: W
authors: Ye
mesh_terms: D000071118:ADAMTS7 Protein / Q000235:genetics / Q000378:metabolism; D045784:Abietanes / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000070614:Nucleus Pulposus / Q000166:cytology*; D051381:Rats; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D045784:Abietanes; D001549:Benzamides; D016328:NF-kappa B; C505226:SM 7368; D016329:Sp1 Transcription Factor; D013844:Thiazoles; D018808:Transcription Factor AP-1; C021751:tanshinone; D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human
keywords: Inflammatory cytokines; Intervertebral disc degeneration; NF-κB signaling pathway; Nucleus pulposus