Evidence map›Paper›PMID 29285799›Full record

ArticleJournal of pineal research2018

Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis.

Sifat Maria, Rebekah M Samsonraj, Fahima Munmun, Jessica Glas, Maria Silvestros, Mary P Kotlarczyk, Ryan Rylands, Amel Dudakovic, Andre J van Wijnen, Larry T Enderby and 7 more

Open access · greenAbstract read
In one paragraph

Article in Journal of pineal research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 147 citations in OpenAlex.

  1. Evaluation ofPeerJ · 2024
    Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. The Effect of Melatonin on Periodontitis.International journal of molecular sciences · 2021
    Trial
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
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  17. Article
  18. Biopolymeric Scaffolds with Melatonin for Tissue Engineering-A Review.International journal of molecular sciences · 2025
    Review
  19. Article
  20. Review

29 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 1 country.

Sifat MariaDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Rebekah M SamsonrajDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Fahima MunmunDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Jessica GlasDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Maria SilvestrosDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Mary P KotlarczykDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Ryan RylandsDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Amel DudakovicDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Andre J van WijnenDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Larry T EnderbyEnderby Healthcare/Legal Consulting, LLC, Pittsburgh, PA, USA.
Holly LassilaDivision of Clinical Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Bala DoddaDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Vicki L DavisDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.
Judy BalkWest Penn/Allegheny Health System, Drexel University and Temple University, Pittsburgh, PA, USA.
Matt BurowCenter for Stem Cell Research and Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
Bruce A BunnellCenter for Stem Cell Research and Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
Paula A Witt-EnderbyDivision of Pharmaceutical, Administrative and Social Sciences, Duquesne University School of Pharmacy, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1844-4457
Duquesne University · USMayo Clinic · USTulane University · USAllegheny Health Network · USVA Pittsburgh Healthcare System · US

Funding

Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
The Role of MEK5 in Melatonin-induced Osteoblast and Osteoclast DifferentiationR15AR068603 · NIAMS · DUQUESNE UNIVERSITY · PI WITT-ENDERBY, PAULA ANN · 2016 to 2016
$364k
Planning a Trial of Novel Footwear for Knee OsteoarthritisR34AR068605 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FELSON, DAVID TOBIN · 2016 to 2016
$362k
NIAMS NIH HHS R01 AR049069NIAMS NIH HHS R15 AR068603NIAMS NIH HHS R34 AR068605
6 · The paper itself

Abstract

The Melatonin Osteoporosis Prevention Study (MOPS) demonstrated that nightly melatonin resulted in a time-dependent decrease in equilibrium ratios of serum osteoclasts and osteoblasts in perimenopausal women. This study examines mechanisms related to the ratios of osteoblasts and osteoclasts using coculture models (transwell or layered) of human mesenchymal stem cell (MSC) and human peripheral blood monocytes (PBMCs). Human MSC/PBMC cocultures exposed to melatonin in osteogenic (OS+) medium for 21 days induced osteoblast differentiation and mineralization; however, only in layered cocultures did melatonin inhibit osteoclastogenesis. Melatonin effects were mediated through MT2 melatonin receptors, MEK1/2, and MEK5. In layered but not transwell cocultures, melatonin increased OPG:RANKL ratios by inhibiting RANKL, suggesting that contact with osteoclasts during osteoblastogenesis inhibits RANKL secretion. Melatonin modulated expression of ERK1/2, ERK5, β1 integrin, GLUT4, and IRβ that was dependent upon the type of coculture; however, in both cultures, melatonin increased RUNX2 and decreased PPARγ expression, indicating a role for metabolic processes that control osteogenic vs adipogenic cell fates of MSCs. Furthermore, melatonin also has osteoblast-inducing effects on human adipose-derived MSCs. In vivo, one-year nightly melatonin (15 mg/L) given to neu female mice in their drinking water increased pErk1/2, pErk5, Runx2, and Opg and Rankl levels in bone consistent with melatonin's already reported bone-enhancing effects. Finally, analysis of daily logs from the MOPS demonstrated a significant improvement in mood and perhaps sleep quality in women receiving melatonin vs placebo. The osteoblast-inducing, bone-enhancing effects of melatonin and improvement in quality of life suggest that melatonin is a safe and effective bone loss therapy.

Indexed as

AnimalsAntioxidantsCell DifferentiationCells, CulturedCoculture TechniquesHumansMAP Kinase Kinase KinasesMelatoninMesenchymal Stem CellsMiceMonocytesOsteoblastsOsteoclastsOsteogenesisPerimenopauseQuality of LifeAntioxidantsMAP Kinase Kinase KinasesMelatoninReceptor, Melatonin, MT2adipocytesGLUT4MEK1/2MEK5melatoninmesenchymal stem cellsMT2 melatonin receptorosteoblastsosteoclastsPPARγ

Identifiers

PMID29285799
PMCPMC6711668
OpenAlexW2781142978

What OpenQuestion holds

Textmetadata
LicenceTDM
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.