PMID- 16368252
OWN - NLM
STAT- MEDLINE
DCOM- 20061017
LR  - 20161018
IS  - 1063-4584 (Print)
IS  - 1063-4584 (Linking)
VI  - 14
IP  - 5
DP  - 2006 May
TI  - Downregulation of inhibitor of apoptosis proteins in apoptotic human chondrocytes 
      treated with tumor necrosis factor-alpha and actinomycin D.
PG  - 435-41
AB  - OBJECTIVE: Apoptosis of chondrocytes plays a pivotal role in cartilage 
      degeneration. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory 
      cytokine and has been assumed to cause the degradation of human cartilage. To 
      investigate the mechanisms of TNF-alpha-mediated apoptosis of human chondrocytes 
      from a point of view of the balance between the caspase-cascade and the 
      expression of inhibitor of apoptosis proteins (IAPs), although both of them are 
      induced with TNF-signals. METHODS: The expression of TNF-receptors (TNF-Rs) in 
      normal human articular chondrocyte (NHAC-kn) was examined with 
      immunocytochemistry. Subconfluent cultures of NHAC-kn were tested with TNF-alpha 
      and/or actinomycin D (actD), and the induction of apoptosis was evaluated by the 
      frequency of apoptotic cells visualized with nuclear staining using Hoechst 
      33342. The activation of caspases and the expression of IAPs were examined with 
      Western blot analyses. RESULTS: NHAC-kn expressed TNF-R1 and -R2. When NHAC-kn 
      was treated with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml) for 24 h, the 
      frequency of apoptotic cells increased to more than 25%. TNF-alpha alone, 
      however, induced the apoptosis insufficiently (up to 8.3%), even when used at the 
      concentration of 100 ng/ml for 48 h. In apoptotic human chondrocytes induced with 
      TNF-alpha (10 ng/ml) and actD (0.2 microg/ml), the caspase-3, -8, and -9 were 
      activated and the protein expression of XIAP and c-IAP1 decreased. CONCLUSIONS: 
      In apoptotic human chondrocytes induced with TNF-alpha and actD, the balance 
      between caspase activation and IAPs' expression lay with the executioner caspase 
      (caspase-3) and led to decreased expression of XIAP and c-IAP1.
FAU - Yoshimura, F
AU  - Yoshimura F
AD  - Department of Pathology, Iwate Medical University School of Medicine, 19-1 
      Uchimaru, Morioka 020-8505, Japan.
FAU - Kanno, H
AU  - Kanno H
FAU - Uzuki, M
AU  - Uzuki M
FAU - Tajima, K
AU  - Tajima K
FAU - Shimamura, T
AU  - Shimamura T
FAU - Sawai, T
AU  - Sawai T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051220
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Blotting, Western/methods
MH  - Caspases/metabolism
MH  - Cells, Cultured
MH  - Chondrocytes/*drug effects
MH  - Dactinomycin/*pharmacology
MH  - Down-Regulation/physiology
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Protein Synthesis Inhibitors/*pharmacology
MH  - Receptors, Tumor Necrosis Factor/analysis
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2005/12/22 09:00
MHDA- 2006/10/18 09:00
CRDT- 2005/12/22 09:00
PHST- 2005/09/29 00:00 [received]
PHST- 2005/11/07 00:00 [accepted]
PHST- 2005/12/22 09:00 [pubmed]
PHST- 2006/10/18 09:00 [medline]
PHST- 2005/12/22 09:00 [entrez]
AID - S1063-4584(05)00315-8 [pii]
AID - 10.1016/j.joca.2005.11.003 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2006 May;14(5):435-41. doi: 10.1016/j.joca.2005.11.003. 
      Epub 2005 Dec 20.