Evidence map›Paper›PMID 29415886›Full record

ArticleJCI insight2018

Osteoblastic heparan sulfate regulates osteoprotegerin function and bone mass.

Satoshi Nozawa, Toshihiro Inubushi, Fumitoshi Irie, Iori Takigami, Kazu Matsumoto, Katsuji Shimizu, Haruhiko Akiyama, Yu Yamaguchi

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

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  9. Review
  10. An analysis of osteoporosis in patients with hereditary multiple exostoses.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020
    Article
  11. Article
  12. Article
  13. Antiresorptive activity of osteoprotegerin requires an intact heparan sulfate-binding site.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  14. Mesenchymal Cell-Derived Juxtacrine Wnt1 Signaling Regulates Osteoblast Activity and Osteoclast Differentiation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019
    Article
  15. Article
  16. Article
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

8 authors at 2 institutions in 2 countries.

Satoshi NozawaHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Toshihiro InubushiHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Fumitoshi IrieHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Iori TakigamiDepartment of Orthopedic Surgery, Gifu University, Gifu, Japan.
Kazu MatsumotoDepartment of Orthopedic Surgery, Gifu University, Gifu, Japan.
Katsuji ShimizuDepartment of Orthopedic Surgery, Gifu University, Gifu, Japan.
Haruhiko AkiyamaDepartment of Orthopedic Surgery, Gifu University, Gifu, Japan.
Yu YamaguchiHuman Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Gifu University · JPSanford Burnham Prebys Medical Discovery Institute · US

Funding

Heparan Sulfate in Skeletal Development and DiseasesR01AR055670 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YAMAGUCHI, YU · 2008 to 2018
$4.9M
NIAMS NIH HHS R01 AR055670
6 · The paper itself

Abstract

Bone remodeling is a highly coordinated process involving bone formation and resorption, and imbalance of this process results in osteoporosis. It has long been recognized that long-term heparin therapy often causes osteoporosis, suggesting that heparan sulfate (HS), the physiological counterpart of heparin, is somehow involved in bone mass regulation. The role of endogenous HS in adult bone, however, remains unclear. To determine the role of HS in bone homeostasis, we conditionally ablated Ext1, which encodes an essential glycosyltransferase for HS biosynthesis, in osteoblasts. Resultant conditional mutant mice developed severe osteopenia. Surprisingly, this phenotype is not due to impairment in bone formation but to enhancement of bone resorption. We show that osteoprotegerin (OPG), which is known as a soluble decoy receptor for RANKL, needs to be associated with the osteoblast surface in order to efficiently inhibit RANKL/RANK signaling and that HS serves as a cell surface binding partner for OPG in this context. We also show that bone mineral density is reduced in patients with multiple hereditary exostoses, a genetic bone disorder caused by heterozygous mutations of Ext1, suggesting that the mechanism revealed in this study may be relevant to low bone mass conditions in humans.

Indexed as

AdultAnimalsBone and BonesBone DensityBone Diseases, MetabolicBone ResorptionCell DifferentiationCells, CulturedCHO CellsCoculture TechniquesCricetulusDisease Models, AnimalExostoses, Multiple HereditaryExostosin 1FemaleHEK293 CellsExostosin 1Heparan SulfateN-AcetylglucosaminyltransferasesOsteoprotegerinRecombinant ProteinsTNFRSF11B protein, humanTnfrsf11b protein, mouseBone BiologyOsteoclast/osteoblast biologyOsteoporosisProteoglycans

Identifiers

PMID29415886
PMCPMC5821205
OpenAlexW2786857780

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.