Evidence map›Paper›PMID 36379392›Full record

ArticleOsteoarthritis and cartilage2023

A novel whole "Joint-in-Motion" device reveals a permissive effect of high glucose levels and mechanical stress on joint destruction.

C K Hui Mingalone, C R Nehme, Y Chen, J Liu, B N Longo, K D Garvey, S M Covello, H C Nielsen, T James, W C Messner and 1 more

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

Article in Osteoarthritis and cartilage, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 45% 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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

11 authors at 1 institution in 1 country.

C K Hui MingaloneProgram in Cell, Molecular, and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
C R NehmeDepartment of Mechanical Engineering, Tufts University, Medford, MA 02155, USA.
Y ChenProgram in Pharmacology and Drug Development, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
J LiuDepartment of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.
B N LongoDepartment of Mechanical Engineering, Tufts University, Medford, MA 02155, USA.
K D GarveyProgram in Pharmacology and Drug Development, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
S M CovelloProgram in Pharmacology and Drug Development, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
H C NielsenProgram in Cell, Molecular, and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA; Department of Pediatrics, Tufts Medical Center, Boston, MA 02111, USA.
T JamesDepartment of Mechanical Engineering, Tufts University, Medford, MA 02155, USA.
W C MessnerDepartment of Mechanical Engineering, Tufts University, Medford, MA 02155, USA. Electronic address: bmessner@andrew.cmu.edu.
L ZengProgram in Cell, Molecular, and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA; Program in Pharmacology and Drug Development, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA; Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA. Electronic address: Li.Zeng@tufts.edu.
Tufts University · US

Funding

Wnt7a-Mediated Competence to Resist Osteoarthritis ProgressionR01AR077146 · NIAMS · TUFTS UNIVERSITY BOSTON · PI ZENG, LI · 2021 to 2025
$3.3M
Screening antibiotics using NIR fluorescence imaging for osteoarthritis treatmentR21AR069278 · NIAMS · TUFTS UNIVERSITY BOSTON · PI ZENG, LI · 2016 to 2017
$399k
NIAMS NIH HHS R01 AR077146NIAMS NIH HHS R21 AR069278
6 · The paper itself

Abstract

objectiveOsteoarthritis (OA) has recently been suggested to be associated with diabetes. However, this association often disappears when accounting for body mass index (BMI), suggesting that mechanical stress may be a confounding factor. We investigated the combined influence of glucose level and loading stress on OA progression using a novel whole joint-in-motion (JM) culture system.

designWhole mouse knee joints were placed in an enclosed chamber with culture media and actuated to recapitulate leg movement, with a dynamic stress regimen of 0.5 Hz, 8 h/day for 7 days. These joints were treated with varying levels of glucose and controlled for osmolarity and diffusion. Joint movement and joint space were examined by X-ray fluoroscopy and microCT. Cartilage matrix levels were quantified by blinded Mankin scoring and immunohistochemistry.

resultsCulturing in the JM device facilitated proper leg extension and flexion movements, and adequate mass transport for analyzing the effect of glucose on cartilage. Treatment with higher levels of glucose either via media supplementation or intra-articular injection caused a significant decrease in levels of glycosaminoglycan (GAG) and an increase in aggrecan neoepitope in articular cartilage, but only under dynamic stress. Additionally, collagen II level was slightly reduced by high glucose levels.

conclusionsHigh levels of glucose and dynamic stress have permissive effects on articular cartilage GAG loss and aggrecan degradation, implicating that mechanical stress confounds the association of diabetes with OA. The JM device supports novel investigation of mechanical stress on the integrity of an intact living mouse joint to provide insights into OA pathogenesis.

Indexed as

Cartilage, ArticularOsteoarthritisAggrecansAnimalsCollagenGlycosaminoglycansMiceStress, MechanicalAggrecansCollagenGlycosaminoglycansGlucoseJointMechanical stressMotionMouseOsteoarthritis

Identifiers

PMID36379392
PMCPMC10033281
OpenAlexW4309077221

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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.