Evidence map›Paper›PMID 22227436›Full record

ArticleBone2012

Bone marrow-derived heparan sulfate potentiates the osteogenic activity of bone morphogenetic protein-2 (BMP-2).

Diah S Bramono, Sadasivam Murali, Bina Rai, Ling Ling, Wei Theng Poh, Zophia Xuehui Lim, Gary S Stein, Victor Nurcombe, Andre J van Wijnen, Simon M Cool

Open access · greenAbstract read
In one paragraph

Article in Bone, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

50 citing papers in PubMed, 115 citations in OpenAlex.

  1. Article
  2. Molecular-level understanding of the aging bone and regeneration mechanisms using computational methods.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
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  15. Article
  16. Article
  17. Heparan Sulfate Proteoglycans: Key Mediators of Stem Cell Function.Frontiers in cell and developmental biology · 2020
    Review
  18. Article
  19. Article
  20. 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

10 authors at 4 institutions in 2 countries.

Diah S BramonoStem Cells and Tissue Repair Group, Institute of Medical Biology, A*STAR, Biopolis, Singapore 138648, Singapore.
Sadasivam Murali
Bina Rai
Ling Ling
Wei Theng Poh
Zophia Xuehui Lim
Gary S Stein
Victor Nurcombe
Andre J van Wijnen
Simon M Cool
Agency for Science, Technology and Research · SGInstitute of Medical Biology · SGUniversity of Massachusetts Chan Medical School · USNational University of Singapore · SG

Funding

CONTROL OF OSTEOBLAST PROLIFERATION AND DIFFERENTIATIONR01AR039588 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B., STEIN, GARY S. · 1990 to 2019
$8.0M
Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
NIAMS NIH HHS R01 AR039588NIAMS NIH HHS R01 AR049069
6 · The paper itself

Abstract

Lowering the efficacious dose of bone morphogenetic protein-2 (BMP-2) for the repair of critical-sized bone defects is highly desirable, as supra-physiological amounts of BMP-2 have an increased risk of side effects and a greater economic burden for the healthcare system. To address this need, we explored the use of heparan sulfate (HS), a structural analog of heparin, to enhance BMP-2 activity. We demonstrate that HS isolated from a bone marrow stromal cell line (HS-5) and heparin each enhances BMP-2-induced osteogenesis in C2C12 myoblasts through increased ALP activity and osteocalcin mRNA expression. Commercially available HS variants from porcine kidney and bovine lung do not generate effects as great as HS5. Heparin and HS5 influence BMP-2 activity by (i) prolonging BMP-2 half-life, (ii) reducing interactions between BMP-2 with its antagonist noggin, and (iii) modulating BMP2 distribution on the cell surface. Importantly, long-term supplementation of HS5 but not heparin greatly enhances BMP-2-induced bone formation in vitro and in vivo. These results show that bone marrow-derived HS effectively supports bone formation, and suggest its applicability in bone repair by selectively facilitating the delivery and bioavailability of BMP-2.

Indexed as

AnimalsBiological AvailabilityBone Marrow CellsBone Morphogenetic Protein 2Bone Morphogenetic Protein Receptors, Type ICarrier ProteinsCattleCell DifferentiationCell LineChoristomaChromatography, High Pressure LiquidChromatography, Ion ExchangeCulture Media, ConditionedDisaccharidesDrug SynergismFemaleBone Morphogenetic Protein 2Bone Morphogenetic Protein Receptors, Type ICarrier ProteinsCulture Media, ConditionedDisaccharidesHeparan SulfateHeparinNoggin Protein

Identifiers

PMID22227436
PMCPMC3589980
OpenAlexW2039234206

What OpenQuestion holds

Textmetadata
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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.