PMID- 10671521
OWN - NLM
STAT- MEDLINE
DCOM- 20000321
LR  - 20220409
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 7
DP  - 2000 Feb 18
TI  - Tumor necrosis factor-alpha induces differentiation of and bone resorption by 
      osteoclasts.
PG  - 4858-64
AB  - Osteoclast progenitors differentiate into mature osteoclasts in the presence of 
      receptor activator of NF-kappaB (RANK) ligand on stromal or osteoblastic cells 
      and monocyte macrophage colony-stimulating factor (M-CSF). The soluble RANK 
      ligand induces the same differentiation in vitro without stromal cells. Tumor 
      necrosis factor-alpha (TNF-alpha), a potent cytokine involved in the regulation 
      of osteoclast activity, promotes bone resorption via a primary effect on 
      osteoblasts; however, it remains unclear whether TNF-alpha can also directly 
      induce the differentiation of osteoclast progenitors into mature osteoclasts. 
      This study revealed that TNF-alpha directly induced the formation of 
      tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), 
      which produced resorption pits on bone in vitro in the presence of M-CSF. The 
      bone resorption activity of TNF-alpha-induced MNCs was lower than that of soluble 
      RANK ligand-induced MNCs; however, interleukin-1beta stimulated this activity of 
      TNF-alpha-induced MNCs without an increase in the number of MNCs. In this case, 
      interleukin-1beta did not induce TRAP-positive MNC formation. The osteoclast 
      progenitors expressed TNF receptors, p55 and p75; and the induction of 
      TRAP-positive MNCs by TNF-alpha was inhibited completely by an anti-p55 antibody 
      and partially by an anti-p75 antibody. Our findings presented here are the first 
      to indicate that TNF-alpha is a crucial differentiation factor for osteoclasts. 
      Our results suggest that TNF-alpha and M-CSF play an important role in local 
      osteolysis in chronic inflammatory diseases.
FAU - Azuma, Y
AU  - Azuma Y
AD  - Teijin Institute for Biomedical Research, Teijin Limited, 4-3-2 Asahigaoka, Hino, 
      Tokyo 191-8512, Japan.
FAU - Kaji, K
AU  - Kaji K
FAU - Katogi, R
AU  - Katogi R
FAU - Takeshita, S
AU  - Takeshita S
FAU - Kudo, A
AU  - Kudo A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Bone Marrow Cells/cytology
MH  - *Bone Resorption
MH  - Cell Differentiation/*physiology
MH  - Male
MH  - Mice
MH  - Osteoclasts/*cytology
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2000/02/15 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/02/15 09:00
PHST- 2000/02/15 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/02/15 09:00 [entrez]
AID - S0021-9258(18)30698-7 [pii]
AID - 10.1074/jbc.275.7.4858 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 18;275(7):4858-64. doi: 10.1074/jbc.275.7.4858.