Evidence map›Paper›PMID 25593124›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion.

Yi Zhou, Aron Mohan, Douglas C Moore, Liangjun Lin, Frank Li Zhou, Jay Cao, Qian Wu, Yi-Xian Qin, Anthony M Reginato, Michael G Ehrlich and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Implications of Heterotypic Cell Fusion in Cancer.Advances in experimental medicine and biology · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Aging · 2024
    Article
  8. Review
  9. Osteoclast Methods in Protein Phosphatase Research.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  10. Mechanisms of Cell Fusion in Cancer.Results and problems in cell differentiation · 2024
    Review
  11. From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. The Dark Side of Cell Fusion.International journal of molecular sciences · 2016
    Review
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 8 institutions in 1 country.

Yi Zhou*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Aron Mohan*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Douglas C Moore*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Liangjun Lin*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Frank Li Zhou*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Jay Cao*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Qian Wu*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Yi-Xian Qin*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Anthony M Reginato*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Michael G Ehrlich*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA.
Wentian Yang*Stem Cell Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Orthopaedics, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA; Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA; Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA; U.S. Department of Agriculture Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota, USA; Department of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA; and Division of Rheumatology, Brown University Alpert Medical School and Rhode Island Hospital, Providence, Rhode Island, USA wyang@lifespan.org.
Rhode Island Hospital · USBrown University · USCalifornia Institute of Technology · USGrand Forks Human Nutrition Research Center · USHarvard University · USState University of New York · USStony Brook University · USUConn Health · US

Funding

COBRE for Skeletal Health and RepairP20GM104937 · NIGMS · RHODE ISLAND HOSPITAL · PI CHEN, QIAN · 2012 to 2016
$10.8M
Stem Cell Biology: New Directions in Clinical and Basic ResearchP20GM103468 · NIGMS · RHODE ISLAND HOSPITAL · PI QUESENBERRY, PETER J. · 2012 to 2013
$4.5M
Functional Fluid Flow Regulated Bone RegenerationR01AR061821 · NIAMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI QIN, YI-XIAN · 2012 to 2016
$1.7M
Shp2 in Osteoclastogenesis and Bone RemodelingR21AR057156 · NIAMS · RHODE ISLAND HOSPITAL · PI YANG, WENTIAN · 2009 to 2010
$378k
NIAMS NIH HHS R01 AR061821NIAMS NIH HHS R21 AR057156NIAMS NIH HHS R21AR57156NIGMS NIH HHS P20 GM103468NIGMS NIH HHS P20 GM104937
6 · The paper itself

Abstract

Genes that regulate osteoclast (OC) development and function in both physiologic and disease conditions remain incompletely understood. Shp2 (the Src homology-2 domain containing protein tyrosine phosphatase 2), a ubiquitously expressed cytoplasmic protein tyrosine phosphatase, is implicated in regulating M-CSF and receptor activator of nuclear factor-κB ligand (RANKL)-evoked signaling; its role in osteoclastogenesis and bone homeostasis, however, remains unknown. Using a tissue-specific gene knockout approach, we inactivated Shp2 expression in murine OCs. Shp2 mutant mice are phenotypically osteopetrotic, featuring a marked increase of bone volume (BV)/total volume (TV) (+42.8%), trabeculae number (Tb.N) (+84.1%), structure model index (+119%), and a decrease of trabecular thickness (Tb.Th) (-34.1%) and trabecular spacing (Tb.Sp) (-41.0%). Biochemical analyses demonstrate that Shp2 is required for RANKL-induced formation of giant multinucleated OCs by up-regulating the expression of nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), a master transcription factor that is indispensable for terminal OC differentiation. Shp2 deletion, however, has minimal effect on M-CSF-dependent survival and proliferation of OC precursors. Instead, its deficiency aborts the fusion of OC precursors and formation of multinucleated OCs and decreases bone matrix resorption. Moreover, pharmacological intervention of Shp2 is sufficient to prevent preosteoclast fusion in vitro. These findings uncover a novel mechanism through which Shp2 regulates osteoclastogenesis by promoting preosteoclast fusion. Shp2 or its signaling partners could potentially serve as pharmacological targets to regulate the population of OCs locally and/or systematically, and thus treat OC-related diseases, such as periprosthetic osteolysis and osteoporosis.

Indexed as

AnimalsApoptosisBlotting, WesternBone MarrowCell DifferentiationCell ProliferationCells, CulturedFemaleHumansMaleMiceMice, KnockoutMice, TransgenicNFATC Transcription FactorsOsteoclastsOsteopetrosisNFATC Transcription FactorsProtein Tyrosine Phosphatase, Non-Receptor Type 11Ptpn11 protein, mouseRANK LigandRNA, MessengerM-CSFNfatc1RANKL

Identifiers

PMID25593124
PMCPMC4415019
OpenAlexW1987159215

What OpenQuestion holds

Textmetadata
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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.