PMID- 16632109
OWN - NLM
STAT- MEDLINE
DCOM- 20060829
LR  - 20220330
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 40
IP  - 9
DP  - 2006 May 1
TI  - Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing 
      nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by 
      receptor activator of nuclear factor-kappaB ligand and tumor necrosis 
      factor-alpha.
PG  - 1483-93
AB  - The relationship between oxidative stress and bone mineral density or 
      osteoporosis has recently been reported. As bone loss occurring in osteoporosis 
      and inflammatory diseases is primarily due to increases in osteoclast number, 
      reactive oxygen species (ROS) may be relevant to osteoclast differentiation, 
      which requires receptor activator of nuclear factor-kappaB ligand (RANKL). Tumor 
      necrosis factor-alpha (TNF-alpha) frequently present in inflammatory conditions 
      has a profound synergy with RANKL in osteoclastogenesis. In this study, we 
      investigated the effects of alpha-lipoic acid (alpha-LA), a strong antioxidant 
      clinically used for some time, on osteoclast differentiation and bone resorption. 
      At concentrations showing no growth inhibition, alpha-LA potently suppressed 
      osteoclastogenesis from bone marrow-derived precursor cells driven either by a 
      high-dose RANKL alone or by a low-dose RANKL plus TNF-alpha (RANKL/TNF-alpha). 
      alpha-LA abolished ROS elevation by RANKL or RANKL/TNF-alpha and inhibited 
      NF-kappaB activation in osteoclast precursor cells. Specifically, alpha-LA 
      reduced DNA binding of NF-kappaB but did not inhibit IKK activation. Furthermore, 
      alpha-LA greatly suppressed in vivo bone loss induced by RANKL or TNF-alpha in a 
      calvarial remodeling model. Therefore, our data provide evidence that ROS plays 
      an important role in osteoclast differentiation through NF-kappaB regulation and 
      the antioxidant alpha-lipoic acid has a therapeutic potential for bone erosive 
      diseases.
FAU - Kim, Hyon Jong
AU  - Kim HJ
AD  - Department of Cell and Developmental Biology, Brain Korea 21 Program, and Dental 
      Research Institute, Seoul National University School of Dentistry, 28 
      Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea.
FAU - Chang, Eun-Ju
AU  - Chang EJ
FAU - Kim, Hyun-Man
AU  - Kim HM
FAU - Lee, Seung Bok
AU  - Lee SB
FAU - Kim, Hyun-Duck
AU  - Kim HD
FAU - Su Kim, Ghi
AU  - Su Kim G
FAU - Kim, Hong-Hee
AU  - Kim HH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051209
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Antioxidants)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RANK Ligand)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 73Y7P0K73Y (Thioctic Acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Blotting, Western
MH  - Bone Resorption/*metabolism
MH  - Carrier Proteins/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Electrophoretic Mobility Shift Assay
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Microscopy, Confocal
MH  - NF-kappa B
MH  - Osteoclasts/cytology/*drug effects
MH  - RANK Ligand
MH  - Reactive Oxygen Species
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thioctic Acid/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2006/04/25 09:00
MHDA- 2006/08/30 09:00
CRDT- 2006/04/25 09:00
PHST- 2005/07/07 00:00 [received]
PHST- 2005/10/03 00:00 [revised]
PHST- 2005/10/26 00:00 [accepted]
PHST- 2006/04/25 09:00 [pubmed]
PHST- 2006/08/30 09:00 [medline]
PHST- 2006/04/25 09:00 [entrez]
AID - S0891-5849(05)00703-3 [pii]
AID - 10.1016/j.freeradbiomed.2005.10.066 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2006 May 1;40(9):1483-93. doi: 
      10.1016/j.freeradbiomed.2005.10.066. Epub 2005 Dec 9.