Evidence map›Paper›PMID 27759007›Full record

ArticleNature communications2016

SIKs control osteocyte responses to parathyroid hormone.

Marc N Wein, Yanke Liang, Olga Goransson, Thomas B Sundberg, Jinhua Wang, Elizabeth A Williams, Maureen J O'Meara, Nicolas Govea, Belinda Beqo, Shigeki Nishimori and 16 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
8.4field-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

100 citing papers in PubMed, 160 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Advances in Parathyroid Hormone-based medicines.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025
    Review
  8. Article
  9. Article
  10. A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Review
  12. Control of alveolar bone development, homeostasis, and socket healing by salt-inducible kinases.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 8 institutions in 4 countries.

Marc N WeinEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Yanke LiangDana Farber Cancer Institute, Department of Biologic Chemistry and Molecular Pharmacology, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
Olga GoranssonDepartment of Experimental Medical Sciences, Lund University, Box 188, SE-221 00 Lund, Sweden.
Thomas B SundbergCenter for the Development of Therapeutics, Broad Institute, 415 Main Street, Cambridge, Massachusetts 02142, USA.
Jinhua WangDana Farber Cancer Institute, Department of Biologic Chemistry and Molecular Pharmacology, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
Elizabeth A WilliamsEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Maureen J O'MearaEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Nicolas GoveaEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Belinda BeqoEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Shigeki NishimoriEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Kenichi NaganoHarvard School of Dental Medicine, Department of Oral Medicine, Infection, and Immunity, 188 Longwood Avenue, Boston, Massachusetts 02115, US.
Daniel J BrooksEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Janaina S MartinsEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Braden CorbinEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Anthony AnselmoDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
Ruslan SadreyevDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
Joy Y WuDivision of Endocrinology, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Dr a175, Stanford, California 94305, USA.
Kei SakamotoMRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Marc ForetzINSERM U1016, Institut Cochin, CNRS UMR8104, Universite Paris Descartes Sorbonne Pairs Cite, Paris 75013, France.
Ramnik J XavierGastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Roland BaronEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Mary L BouxseinEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Thomas J GardellaEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Paola Divieti-PajevicHenry M. Goldman School of Dental Medicine, Boston University, 100 E Newton Street, Boston, Massachusetts 02118, USA.
Nathanael S GrayDana Farber Cancer Institute, Department of Biologic Chemistry and Molecular Pharmacology, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.ORCID 0000-0001-5354-7403
Henry M KronenbergEndocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Harvard University · USBeth Israel Deaconess Medical Center · USBroad Institute · USBoston University · USDélégation Paris 5 · FRLund University · SEStanford University · USUniversity of Dundee · GB

Funding

Tissue Phenotyping CoreP01DK011794 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JUEPPNER, HARALD W. · 1986 to 2023
$44.4M
Skeletal Phenotyping CoreP30AR066261 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI KRONENBERG, HENRY M. · 2014 to 2018
$3.5M
Dissecting the roles of class IIa HDACs in osteocyte biologyK08AR067285 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI WEIN, MARC NATHAN · 2015 to 2019
$698k
Sclerostin and Gsalpha signaling in osteoblastsR03AR059942 · NIAMS · STANFORD UNIVERSITY · PI WU, JOY Y · 2010 to 2012
$235k
NIAMS NIH HHS K08 AR067285NIAMS NIH HHS P30 AR066261NIAMS NIH HHS R03 AR059942NIDDK NIH HHS P01 DK011794
6 · The paper itself

Abstract

Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.

Indexed as

Active Transport, Cell NucleusAdaptor Proteins, Signal TransducingAnimalsBone and BonesGene Expression RegulationGlycoproteinsHistone DeacetylasesHumansIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutOsteocytesOsteogenesisParathyroid HormonePhosphorylationPrimary Cell CultureAdaptor Proteins, Signal TransducingCrtc2 protein, mouseGlycoproteinsHdac5 protein, mouseHistone DeacetylasesIntercellular Signaling Peptides and ProteinsParathyroid HormoneProtein IsoformsProtein Kinase InhibitorsProtein Serine-Threonine KinasesRANK LigandRNA, Small Interferingsalt-inducible kinase-2, mouseSost protein, mouseTnfsf11 protein, mouseTranscription Factors

Identifiers

PMID27759007
PMCPMC5075806
OpenAlexW2538581714

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.