Evidence map›Paper›PMID 18589009›Full record

ArticleBone2008

Heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation.

A J Brown, M Alicknavitch, S S D'Souza, T Daikoku, C B Kirn-Safran, D Marchetti, D D Carson, M C Farach-Carson

Open access · greenAbstract read
In one paragraph

Article in Bone, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Exploring Growth Pattern and Candidate Genes for Chicken Spur.Animals : an open access journal from MDPI · 2026
    Article
  2. Schwartz-Jampel Syndrome Type 1: Compound Heterozygosity of Two Novel VariantsJournal of clinical research in pediatric endocrinology · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Single molecule force measurements of perlecan/HSPG2: A key component of the osteocyte pericellular matrix.Matrix biology : journal of the International Society for Matrix Biology · 2016
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Border patrol: insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders.Matrix biology : journal of the International Society for Matrix Biology · 2014
    Review
  18. Heparan sulfate in skeletal development, growth, and pathology: the case of hereditary multiple exostoses.Developmental dynamics : an official publication of the American Association of Anatomists · 2013
    Review
  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

8 authors at 3 institutions in 1 country.

A J BrownDepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
M Alicknavitch
S S D'Souza
T Daikoku
C B Kirn-Safran
D Marchetti
D D Carson
M C Farach-Carson
University of Delaware · USBaylor College of Medicine · USVanderbilt University Medical Center · US

Funding

Prostate Cancer Bone Metastasis: Biology and TargetingP01CA098912 · NCI · EMORY UNIVERSITY · PI ZAYZAFOON, MAJD · 2003 to 2019
$24.0M
VALGUS BRACING FOR MEDIAL LAXITY IN PATIENTS WITH OSTEOARTHRITISP20RR016458 · NCRR · UNIVERSITY OF DELAWARE · PI RUDOLPH, KATHERINE S · 2002 to 2011
$18.9M
ACL Injured Knee: MRI and Biomechanical ModelingR01AR046386 · NIAMS · UNIVERSITY OF DELAWARE · PI BUCHANAN, THOMAS S · 1999 to 2011
$2.8M
PERLECAN AND CHONDROGENESISR01DE013542 · NIDCR · UNIVERSITY OF DELAWARE · PI CARSON, DANIEL D. · 2001 to 2004
$1.1M
NCI NIH HHS CA 098912NCI NIH HHS P01 CA098912NCRR NIH HHS P20 RR 016458NCRR NIH HHS P20 RR016458NIAMS NIH HHS R01 AR046386NIDCR NIH HHS DE 13542NIDCR NIH HHS R01 DE013542
6 · The paper itself

Abstract

Endochondral bone formation is a highly orchestrated process involving coordination among cell-cell, cell-matrix and growth factor signaling that eventually results in the production of mineralized bone from a cartilage template. Chondrogenic and osteogenic differentiation occur in sequence during this process, and the temporospatial patterning clearly requires the activities of heparin binding growth factors and their receptors. Heparanase (HPSE) plays a role in osteogenesis, but the mechanism by which it does so is incompletely understood. We used a combination of ex vivo and in vitro approaches and a well described HPSE inhibitor, PI-88 to study HPSE in endochondral bone formation. In situ hybridization and immunolocalization with HPSE antibodies revealed that HPSE is expressed in the peri-chondrium, peri-osteum, and at the chondro-osseous junction, all sites of key signaling events and tissue morphogenesis. Transcripts encoding Hpse also were observed in the pre-hypertrophic zone. Addition of PI-88 to metatarsals in organ culture reduced growth and suggested that HPSE activity aids the transition from chondrogenic to osteogenic processes in growth of long bones. To study this, we used high density cultures of ATDC5 pre-chondrogenic cells grown under conditions favoring chondrogenesis or osteogenesis. Under chondrogenic conditions, HPSE/Hpse was expressed at high levels during the mid-culture period, at the onset of terminal chondrogenesis. PI-88 addition reduced chondrogenesis and accelerated osteogenesis, including a dramatic up-regulation of osteocalcin levels. In normal growth medium, addition of PI-88 reduced migration of ATDC-5 cells, suggesting that HPSE facilitates cartilage replacement by bone at the chondro-osseous junction by removing the HS component of proteoglycans, such as perlecan/HSPG2, that otherwise prevent osteogenic cells from remodeling hypertrophic cartilage.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsCell Line, TumorCell MovementChondrocytesChondrogenesisDose-Response Relationship, DrugEnzyme ActivationGlucuronidaseHeparanaseImmunoblottingImmunohistochemistryIn Situ HybridizationMiceMice, Inbred C57BLOligosaccharidesGlucuronidaseHeparanaseOligosaccharidesphosphomannopentaose sulfate

Identifiers

PMID18589009
PMCPMC2621444
OpenAlexW2150433437

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.