Evidence map›Paper›PMID 19299513›Full record

ArticleThe Journal of biological chemistry2009

Trolox prevents osteoclastogenesis by suppressing RANKL expression and signaling.

Jong-Ho Lee, Ha-Neui Kim, Daum Yang, Kyoungsuk Jung, Hyun-Man Kim, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Nutrients · 2025
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  4. Article
  5. Article
  6. Article
  7. Tocotrienol regulates osteoclastogenesis in rheumatoid arthritis.The Korean journal of internal medicine · 2021
    Article
  8. Article
  9. Review
  10. Article
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  12. Article
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  14. Article
  15. Article
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  17. Article
  18. Water extract ofIntegrative medicine research · 2015
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jong-Ho LeeDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Ha-Neui KimDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Daum YangDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Kyoungsuk JungDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Hyun-Man KimDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Hong-Hee KimDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Hyunil HaDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea. Electronic address: hyunil74@hotmail.com.
Zang Hee LeeDepartment of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea. Electronic address: zang1959@snu.ac.kr.
Seoul National University Dental Hospital · KRSeoul National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Excessive receptor activator of NF-kappaB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. Thus, down-regulation of RANKL expression or its downstream signals may be a therapeutic approach to the treatment of pathological bone loss. In this study, we investigated the effects of Trolox, a water-soluble vitamin E analogue, on osteoclastogenesis and RANKL signaling. Trolox potently inhibited interleukin-1-induced osteoclast formation in bone marrow cell-osteoblast coculture by abrogating RANKL induction in osteoblasts. This RANKL reduction was attributed to the reduced production of prostaglandin E(2) via a down-regulation of cyclooxygenase-2 activity. We also found that Trolox inhibited osteoclast formation from bone marrow macrophages induced by macrophage colony-stimulating factor plus RANKL in a reversible manner. Trolox was effective only when present during the early stage of culture, which implies that it targets early osteoclast precursors. Pretreatment with Trolox did not affect RANKL-induced early signaling pathways, including MAPKs, NF-kappaB, and Akt. We found that Trolox down-regulated the induction by RANKL of c-Fos protein by suppressing its translation. Ectopic overexpression of c-Fos rescued the inhibition of osteoclastogenesis by Trolox in bone marrow macrophages. Trolox also suppressed interleukin-1-induced osteoclast formation and bone loss in mouse calvarial bone. Taken together, our findings indicate that Trolox prevents osteoclast formation and bone loss by inhibiting both RANKL induction in osteoblasts and c-Fos expression in osteoclast precursors.

Indexed as

AnimalsAntioxidantsBone Marrow CellsCells, CulturedChromansDinoprostoneGene Expression RegulationHumansMiceOsteoclastsProtein BiosynthesisProto-Oncogene Proteins c-fosRANK LigandSignal TransductionStem Cells6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acidAntioxidantsChromansDinoprostoneProto-Oncogene Proteins c-fosRANK LigandTNFSF11 protein, humanTnfsf11 protein, mouse

Identifiers

PMID19299513
PMCPMC2679474
OpenAlexW2010264483

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.