PMID- 15823554
OWN - NLM
STAT- MEDLINE
DCOM- 20050705
LR  - 20091119
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 330
IP  - 4
DP  - 2005 May 20
TI  - Tumor necrosis factor-alpha induces differentiation of human peripheral blood 
      mononuclear cells into osteoclasts through the induction of p21(WAF1/Cip1).
PG  - 1080-6
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that 
      mediates inflammation and induces bone loss caused by excessive bone resorption 
      by osteoclasts. The interaction of TNF-alpha with its receptor activates several 
      signal transduction pathways, including those of mitogen-activated protein (MAP) 
      kinases (p38, JNK, and ERK) and NF-kappaB. Signaling from these molecules has 
      been shown to play an important role in osteoclastogenesis. In the present study, 
      we investigated the mechanism of TNF-alpha-induced osteoclast differentiation in 
      human peripheral blood mononuclear cells (PBMCs). We found that TNF-alpha alone 
      greatly induced differentiation of PBMCs into osteoclasts. The osteoclast 
      differentiation induced by TNF-alpha was independent of RANKL binding to its 
      receptor RANK on PBMCs. Furthermore, TNF-alpha potently activated p38 MAPK, JNK, 
      and NF-kappaB. Western blotting analysis revealed that p21(WAF1/Cip1), a 
      cyclin-dependent kinase (CDK) inhibitor, is significantly induced upon TNF-alpha 
      stimulation. The induction of p21(WAF1/Cip1) during differentiation is 
      responsible for arrest at G(0)/G(1) phase and associated with the JNK pathway. 
      These results suggest that TNF-alpha regulates osteoclast differentiation through 
      p21(WAF1/Cip1) expression and further shows that these events require JNK 
      activity.
FAU - Kwak, Han Bok
AU  - Kwak HB
AD  - Research Center for Proteineous Materials, Chosun University, Gwangju 501-759, 
      Republic of Korea.
FAU - Jin, Hye-Mi
AU  - Jin HM
FAU - Ha, Hyunil
AU  - Ha H
FAU - Kang, Mi-Jin
AU  - Kang MJ
FAU - Lee, Seung Bok
AU  - Lee SB
FAU - Kim, Hong-Hee
AU  - Kim HH
FAU - Lee, Zang Hee
AU  - Lee ZH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (TNFRSF11A protein, human)
RN  - 0 (TNFSF11 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Carrier Proteins/metabolism
MH  - Cell Cycle Proteins/*biosynthesis
MH  - *Cell Differentiation
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Gene Expression Regulation
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Leukocytes, Mononuclear/*cytology/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - NF-kappa B/metabolism
MH  - Osteoclasts/*cytology/metabolism
MH  - RANK Ligand
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/pharmacology/*physiology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2005/04/13 09:00
MHDA- 2005/07/06 09:00
CRDT- 2005/04/13 09:00
PHST- 2005/03/02 00:00 [received]
PHST- 2005/04/13 09:00 [pubmed]
PHST- 2005/07/06 09:00 [medline]
PHST- 2005/04/13 09:00 [entrez]
AID - S0006-291X(05)00492-4 [pii]
AID - 10.1016/j.bbrc.2005.03.085 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2005 May 20;330(4):1080-6. doi: 
      10.1016/j.bbrc.2005.03.085.