Evidence map›Paper›PMID 28460416›Full record

ArticleJournal of cellular physiology2018

The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis.

Heather Fairfield, Carolyne Falank, Elizabeth Harris, Victoria Demambro, Michelle McDonald, Jessica A Pettitt, Sindhu T Mohanty, Peter Croucher, Ina Kramer, Michaela Kneissel and 2 more

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 2 pooled it
10.9field-weighted citation impact, top 1% 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

101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Bone as an endocrine regulator of lipid and energy metabolism.Reviews in endocrine & metabolic disorders · 2026
    Review
  7. Review
  8. Review
  9. The role of bone in whole-body energy metabolism.Nature reviews. Endocrinology · 2025
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Autophagy: regulating the seesaw of bone-fat balance.Frontiers in cell and developmental biology · 2025
    Review
  15. Bone marrow adipocytes: key players in vascular niches, aging, and disease.Frontiers in cell and developmental biology · 2025
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

41 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

12 authors at 3 institutions in 3 countries.

Heather FairfieldCenter for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.
Carolyne FalankCenter for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.
Elizabeth HarrisCenter for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.
Victoria DemambroCenter for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.
Michelle McDonaldThe Garvan Institute of Medical Research, Sydney, NSW, Australia.
Jessica A PettittThe Garvan Institute of Medical Research, Sydney, NSW, Australia.
Sindhu T MohantyThe Garvan Institute of Medical Research, Sydney, NSW, Australia.
Peter CroucherThe Garvan Institute of Medical Research, Sydney, NSW, Australia.
Ina KramerNovartis Institutes for BioMedical Research, Basel, Switzerland.
Michaela KneisselNovartis Institutes for BioMedical Research, Basel, Switzerland.
Clifford J RosenCenter for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.
Michaela R ReaganCenter for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine.ORCID http://orcid.org/0000-0003-2884-6481
Tufts University · USGarvan Institute of Medical Research · AUNovartis (Switzerland) · CH

Funding

Understanding Factors Influencing COVID-19 Testing and Vaccination in Immigrant Low-income and Homeless Populations and Testing Targeted InterventionsU54GM115516 · NIGMS · MAINEHEALTH · PI Kimberly Luebbers · 2017 to 2026
$51.6M
The role of night shift work in metabolic disorders during and after pregnancyP20GM121301 · NIGMS · MAINEHEALTH · PI Elizabeth Scharnetzki · 2017 to 2026
$25.1M
Interdisciplinary Study of Marrow Adiposity, Mineral Metabolism & Energy BalanceR24DK092759 · NIDDK · MAINEHEALTH · PI HOROWITZ, MARK C, MACDOUGALD, ORMOND A · 2011 to 2019
$13.0M
Progenitor Cell Analysis CoreP30GM106391 · NIGMS · MAINEHEALTH · PI WOJCHOWSKI, DON MICHAEL · 2013 to 2017
$5.7M
Phase III COBRE in Vascular BiologyP30GM103392 · NIGMS · MAINEHEALTH · PI ST. GERMAIN, DONALD L. · 2012 to 2016
$4.7M
NIDDK NIH HHS R24 DK092759NIGMS NIH HHS P20 GM121301NIGMS NIH HHS P30 GM103392NIGMS NIH HHS P30 GM106391NIGMS NIH HHS U54 GM115516
6 · The paper itself

Abstract

The bone marrow niche is a dynamic and complex microenvironment that can both regulate, and be regulated by the bone matrix. Within the bone marrow (BM), mesenchymal stromal cell (MSC) precursors reside in a multi-potent state and retain the capacity to differentiate down osteoblastic, adipogenic, or chondrogenic lineages in response to numerous biochemical cues. These signals can be altered in various pathological states including, but not limited to, osteoporotic-induced fracture, systemic adiposity, and the presence of bone-homing cancers. Herein we provide evidence that signals from the bone matrix (osteocytes) determine marrow adiposity by regulating adipogenesis in the bone marrow. Specifically, we found that physiologically relevant levels of Sclerostin (SOST), which is a Wnt-inhibitory molecule secreted from bone matrix-embedded osteocytes, can induce adipogenesis in 3T3-L1 cells, mouse ear- and BM-derived MSCs, and human BM-derived MSCs. We demonstrate that the mechanism of SOST induction of adipogenesis is through inhibition of Wnt signaling in pre-adipocytes. We also demonstrate that a decrease of sclerostin in vivo, via both genetic and pharmaceutical methods, significantly decreases bone marrow adipose tissue (BMAT) formation. Overall, this work demonstrates a direct role for SOST in regulating fate determination of BM-adipocyte progenitors. This provides a novel mechanism for which BMAT is governed by the local bone microenvironment, which may prove relevant in the pathogenesis of certain diseases involving marrow adipose. Importantly, with anti-sclerostin therapy at the forefront of osteoporosis treatment and a greater recognition of the role of BMAT in disease, these data are likely to have important clinical implications.

Indexed as

Adipogenesis3T3-L1 CellsAdaptor Proteins, Signal TransducingAdipocytesAdipose TissueAdiposityAnimalsBone Marrow CellsCulture Media, ConditionedGlycoproteinsIntercellular Signaling Peptides and ProteinsMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMice, KnockoutAdaptor Proteins, Signal TransducingCulture Media, ConditionedGlycoproteinsIntercellular Signaling Peptides and ProteinsSost protein, mousebone marrow adiposebone marrow microenvironmentosteocyte-derived factorssclerostin

Identifiers

PMID28460416
PMCPMC5664178
OpenAlexW2611616609

What OpenQuestion holds

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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.