Evidence map›Paper›PMID 32107493›Full record

ArticlePloS one2020

Proteolysis and cartilage development are activated in the synovium after surgical induction of post traumatic osteoarthritis.

Ugur M Ayturk, Jakob T Sieker, Carla M Haslauer, Benedikt L Proffen, Manuela H Weissenberger, Matthew L Warman, Braden C Fleming, Martha M Murray

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

8 citing papers in PubMed, 16 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Ugur M AyturkDepartment of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Jakob T SiekerDepartment of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Carla M HaslauerDepartment of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Benedikt L ProffenDepartment of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Manuela H WeissenbergerDepartment of Pathology, Caritas-Hospital Bad Mergentheim, Bad Mergentheim, Germany.
Matthew L WarmanDepartment of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Braden C FlemingDepartment of Orthopaedics, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.ORCID 0000-0002-7841-425X
Martha M MurrayDepartment of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0001-5086-9511
Boston Children's Hospital · USBrown University · USCaritas-Krankenhaus Bad Mergentheim · DE

Funding

Pilot Projects ProgramP30GM122732 · NIGMS · RHODE ISLAND HOSPITAL · PI WEI, LEI · 2017 to 2021
$6.6M
Biologically Enhanced Healing of Autograft ACL Reconstruction.R01AR056834 · NIAMS · RHODE ISLAND HOSPITAL · PI FLEMING, BRADEN C, MURRAY, MARTHA M · 2009 to 2017
$5.8M
The Effect of Age on Functional ACL HealingR01AR054099 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI MURRAY, MARTHA M · 2006 to 2013
$4.8M
Defining Environmental Cues Which Impair Functional ACL HealingF32AR061186 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI HASLAUER, CARLA MARIA · 2012 to 2013
$91k
NIAMS NIH HHS F32 AR061186NIAMS NIH HHS R01 AR054099NIAMS NIH HHS R01 AR056834NIGMS NIH HHS P30 GM122732
6 · The paper itself

Abstract

Anterior cruciate ligament (ACL) transection surgery in the minipig induces post-traumatic osteoarthritis (PTOA) in a pattern similar to that seen in human patients after ACL injury. Prior studies have reported the presence of cartilage matrix-degrading proteases, such as Matrix metalloproteinase-1 (MMP-1) and A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), in the synovial fluid of injured or arthritic joints; however, the tissue origin of these proteases is unknown. The objective of this study was to identify transcriptional processes activated in the synovium after surgical induction of PTOA with ACL transection, and to determine if processes associated with proteolysis were enriched in the synovium after ACL transection. Unilateral ACL transection was performed in adolescent Yucatan minipigs and synovium samples were collected at 1, 5, 9, and 14 days post-injury. Transcriptome-wide gene expression levels were determined using bulk RNA-Sequencing in the surgical animals and control animals with healthy knees. The greatest number of transcripts with significant changes was observed 1 day after injury. These changes were primarily associated with cellular proliferation, consistent with measurements of increased cellularity of the synovium at the two-week time point. At five to 14 days, the expression of transcripts relating to proteolysis and cartilage development was significantly enriched. While protease inhibitor-encoding transcripts (TIMP2, TIMP3) represented the largest fraction of protease-associated transcripts in the uninjured synovium, protease-encoding transcripts (including MMP1, MMP2, ADAMTS4) predominated after surgery. Cartilage development-associated transcripts that are typically not expressed by synovial cells, such as ACAN and COMP, were enriched in the synovium following ACL-transection. The upregulation in both catabolic processes (proteolysis) and anabolic processes (cartilage development) suggests that the synovium plays a complex, balancing role in the early response to PTOA induction.

Indexed as

ProteolysisTranscriptomeAnimalsBiomarkersCartilage, ArticularChondrogenesisMaleOsteoarthritisSwineSwine, MiniatureSynovial MembraneBiomarkers

Identifiers

PMID32107493
PMCPMC7046188
OpenAlexW3007848865

What OpenQuestion holds

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LicenceCC BY
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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.