Evidence map›Paper›PMID 20447377›Full record

ArticleArchives of biochemistry and biophysics2010

Transport and equilibrium uptake of a peptide inhibitor of PACE4 into articular cartilage is dominated by electrostatic interactions.

Sangwon Byun, Micky D Tortorella, Anne-Marie Malfait, Kam Fok, Eliot H Frank, Alan J Grodzinsky

Abstract read
In one paragraph

Article in Archives of biochemistry and biophysics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

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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

6 authors.

Sangwon ByunDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Micky D Tortorella
Anne-Marie Malfait
Kam Fok
Eliot H Frank
Alan J Grodzinsky

Funding

MECHANISMS OF CHONDROCYTE RESPONSE TO MECHANICAL STIMULIR01AR045779 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRODZINSKY, ALAN J. · 1998 to 2008
$2.1M
ELECTROMECHANICS OF CARTILAGE: SYNTHESIS &DEGRADATIIONR01AR033236 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRODZINSKY, ALAN J. · 1986 to 2010
$1.5M
CARTILAGE METABOLIC RESPOSE TO LOADING: TARGET MOLECULESR37AR033236 · NIAMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GRODZINSKY, ALAN J · 1995 to 2004
$1.2M
NIAMS NIH HHS AR33236NIAMS NIH HHS AR45779NIAMS NIH HHS R01 AR033236NIAMS NIH HHS R01 AR045779NIAMS NIH HHS R37 AR033236
6 · The paper itself

Abstract

The availability of therapeutic molecules to targets within cartilage depends on transport through the avascular matrix. We studied equilibrium partitioning and non-equilibrium transport into cartilage of Pf-pep, a 760 Da positively charged peptide inhibitor of the proprotein convertase PACE4. Competitive binding measurements revealed negligible binding of Pf-pep to sites within cartilage. Uptake of Pf-pep depended on glycosaminoglycan charge density, and was consistent with predictions of Donnan equilibrium given the known charge of Pf-pep. In separate transport experiments, the diffusivity of Pf-pep in cartilage was measured to be approximately 1 x 10(-6) cm(2)/s, close to other similarly-sized non-binding solutes. These results suggest that small positively charged therapeutics will have a higher concentration within cartilage than in the surrounding synovial fluid, a desired property for local delivery; however, such therapeutics may rapidly diffuse out of cartilage unless there is additional specific binding to intra-tissue substrates that can maintain enhanced intra-tissue concentration for local delivery.

Indexed as

Amino Acid SequenceAnimalsBiological Transport, ActiveCartilage, ArticularCattleGlycosaminoglycansIn Vitro TechniquesIodine RadioisotopesKineticsModels, BiologicalOligopeptidesProprotein ConvertasesProtease InhibitorsRadiopharmaceuticalsRatsRecombinant ProteinsGlycosaminoglycansIodine RadioisotopesOligopeptidesPcsk6 protein, ratProprotein ConvertasesProtease InhibitorsRadiopharmaceuticalsRecombinant Proteins

Identifiers

PMID20447377
PMCPMC2885539

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Registered trials

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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.