Evidence map›Paper›PMID 28465350›Full record

ArticleThe Journal of biological chemistry2017

Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication.

Yiwen Qin, Yuanzhen Peng, Wei Zhao, Jianping Pan, Hanna Ksiezak-Reding, Christopher Cardozo, Yingjie Wu, Paola Divieti Pajevic, Lynda F Bonewald, William A Bauman and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed, 2 pooled it
10.1field-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

178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 268 citations in OpenAlex.

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  18. Roles of skeletal muscle-derived exosomes in osteoporosis.Journal of translational medicine · 2025
    Review
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118 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

11 authors at 6 institutions in 2 countries.

Yiwen QinFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468.
Yuanzhen PengFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468.
Wei ZhaoFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468.
Jianping PanFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468.
Hanna Ksiezak-RedingNeurology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Christopher CardozoFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468.
Yingjie Wuthe Departments of Medicine.
Paola Divieti Pajevicthe Department of Molecular and Cell Biology, Boston University, Boston, Massachusetts 02215, and.
Lynda F BonewaldIndiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana 46202.
William A BaumanFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468.
Weiping QinFrom the National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York 10468, weiping.qin@mssm.edu weiping.qin@va.gov.
James J. Peters VA Medical Center · USIcahn School of Medicine at Mount Sinai · USBoston University · USDalian Medical University · CNIndiana University – Purdue University Indianapolis · USPain and Rehabilitation Medicine · US

Funding

Osteocytes and Mechano-TransductionUH3AR059655 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DIVIETI PAJEVIC, PAOLA · 2012 to 2014
$1.4M
ES and Androgens in Bone Loss after SCI: Synergistic Effects and MechanismsI01RX000687 · VA · JAMES J PETERS VA MEDICAL CENTER · PI QIN, WEIPING · 2015 to 2017
–
Sclerostin Antagonism and the Osteocytes Role Prevention of Bone Loss after SCII01RX001313 · VA · JAMES J PETERS VA MEDICAL CENTER · PI QIN, WEIPING · 2015 to 2017
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Novel Pharmacological and Non-pharmacological Interventions for Bone Loss in SCII01RX002089 · VA · JAMES J PETERS VA MEDICAL CENTER · PI QIN, WEIPING · 2017 to 2023
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NIAMS NIH HHS UH3 AR059655RRD VA I01 RX000687RRD VA I01 RX001313RRD VA I01 RX002089
6 · The paper itself

Abstract

Muscle and bone are closely associated in both anatomy and function, but the mechanisms that coordinate their synergistic action remain poorly defined. Myostatin, a myokine secreted by muscles, has been shown to inhibit muscle growth, and the disruption of the myostatin gene has been reported to cause muscle hypertrophy and increase bone mass. Extracellular vesicle-exosomes that carry microRNA (miRNA), mRNA, and proteins are known to perform an important role in cell-cell communication. We hypothesized that myostatin may play a crucial role in muscle-bone interactions and may promote direct effects on osteocytes and on osteocyte-derived exosomal miRNAs, thereby indirectly influencing the function of other bone cells. We report herein that myostatin promotes expression of several bone regulators such as sclerostin (SOST), DKK1, and RANKL in cultured osteocytic (Ocy454) cells, concomitant with the suppression of miR-218 in both parent Ocy454 cells and derived exosomes. Exosomes produced by Ocy454 cells that had been pretreated with myostatin could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteoblastic differentiation, and in decreased osteoblastic differentiation via the down-regulation of the Wnt signaling pathway. Importantly, the inhibitory effect of myostatin-modified osteocytic exosomes on osteoblast differentiation is completely reversed by expression of exogenous miR-218, through a mechanism involving miR-218-mediated inhibition of SOST. Together, our findings indicate that myostatin directly influences osteocyte function and thereby inhibits osteoblastic differentiation, at least in part, through the suppression of osteocyte-derived exosomal miR-218, suggesting a novel mechanism in muscle-bone communication.

Indexed as

Cell DifferentiationAdaptor Proteins, Signal TransducingAnimalsCell LineExosomesGlycoproteinsIntercellular Signaling Peptides and ProteinsMiceMicroRNAsMuscle, SkeletalMyostatinOsteocytesRANK LigandWnt Signaling PathwayAdaptor Proteins, Signal TransducingDkk1 protein, mouseGlycoproteinsIntercellular Signaling Peptides and ProteinsMicroRNAsMIRN218 microRNA, mouseMstn protein, mouseMyostatinRANK LigandSost protein, mouseTnfsf11 protein, mouseboneexosome (vesicle)microRNA (miRNA)myostatinosteoblastosteocyteskeletal muscle metabolismWnt signaling

Identifiers

PMID28465350
PMCPMC5491785
OpenAlexW2610851752

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.