PMID- 18923335
OWN - NLM
STAT- MEDLINE
DCOM- 20090210
LR  - 20190104
IS  - 1528-1159 (Electronic)
IS  - 0362-2436 (Linking)
VI  - 33
IP  - 23
DP  - 2008 Nov 1
TI  - Mechanism of signal transduction in tumor necrosis factor-like weak inducer of 
      apoptosis-induced matrix degradation by MMP-3 upregulation in disc tissues.
PG  - 2489-94
LID - 10.1097/BRS.0b013e318186b343 [doi]
AB  - STUDY DESIGN: Molecular biologic and immuno-histologic analyses using in vitro 
      murine intervertebral disc tissue culture. OBJECTIVE: To investigate the role of 
      tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in matrix 
      metalloproteinase 3 (MMP-3) pathway induction, and the effect of TWEAK to induce 
      other cytokines or angiogenesis factors in disc tissues. SUMMARY OF BACKGROUND 
      DATA: We previously demonstrated that TWEAK and its receptor Fn14 were expressed 
      in murine disc tissues. TWEAK induced MMP-3 upregulation and aggrecan 
      downregulation in disc tissues. METHODS: Enzyme-Linked ImmunoSorbent Assay 
      (ELISA), western blot, and immuno-histologic analyses were used to assess the 
      role of TWEAK-induced MMP-3, using murine disc tissue culture. RESULTS: TWEAK 
      induced disc cells to generate MMP-3 as did TNF-alpha and IL-1beta. MMP-3 
      activity was detectable in murine disc cells. MMP-3 induction was markedly 
      inhibited with a c-Jun N-terminal kinase (JNK) inhibitor. Phosphorylation of JNK 
      was also confirmed. Introduction of TWEAK resulted in the degradation of disc 
      matrix in organ disc culture, whereas proteoglycan degradation was markedly 
      abrogated in the presence of an MMP-3 specific inhibitor or a JNK inhibitor. In 
      addition, TWEAK also induced monocyte chemotactic protein (MCP)-1 via the 
      NF-kappaB pathway, as phosphorylation of NF-kappaB was confirmed by western 
      blotting. CONCLUSION: TWEAK plays an important role in MMP-3 induction in murine 
      disc cells via JNK that results in degradation of disc matrix. TWEAK also induces 
      MCP-1, which belongs to the chemokine family that recruits inflammatory cells via 
      the NF-kappaB pathway.
FAU - Wako, Masanori
AU  - Wako M
AD  - Department of Orthopaedic Surgery, Graduate School of Medicine and Engineering, 
      University of Yamanashi, Yamanashi, Japan.
FAU - Ohba, Tetsuro
AU  - Ohba T
FAU - Ando, Takashi
AU  - Ando T
FAU - Arai, Yoshiyasu
AU  - Arai Y
FAU - Koyama, Kensuke
AU  - Koyama K
FAU - Hamada, Yoshiki
AU  - Hamada Y
FAU - Nakao, Atsuhito
AU  - Nakao A
FAU - Haro, Hirotaka
AU  - Haro H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Spine (Phila Pa 1976)
JT  - Spine
JID - 7610646
RN  - 0 (Aggrecans)
RN  - 0 (Anthracenes)
RN  - 0 (Benzamides)
RN  - 0 (Cytokine TWEAK)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tnfsf12 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Necrosis Factors)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - 76145IS906 (N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Aggrecans/metabolism
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - Apoptosis/*drug effects
MH  - Benzamides/pharmacology
MH  - Cytokine TWEAK
MH  - Enzyme Induction
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Matrix/*drug effects/metabolism
MH  - Flavonoids/pharmacology
MH  - Immunoenzyme Techniques
MH  - Intervertebral Disc/*drug effects/metabolism
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Recombinant Proteins/pharmacology
MH  - *Signal Transduction
MH  - Tissue Culture Techniques
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Tumor Necrosis Factors/*metabolism/pharmacology
MH  - Up-Regulation
EDAT- 2008/10/17 09:00
MHDA- 2009/02/12 09:00
CRDT- 2008/10/17 09:00
PHST- 2008/10/17 09:00 [pubmed]
PHST- 2009/02/12 09:00 [medline]
PHST- 2008/10/17 09:00 [entrez]
AID - 10.1097/BRS.0b013e318186b343 [doi]
PST - ppublish
SO  - Spine (Phila Pa 1976). 2008 Nov 1;33(23):2489-94. doi: 
      10.1097/BRS.0b013e318186b343.