Evidence map›Paper›PMID 36075514›Full record

ArticleOsteoarthritis and cartilage2022

Early ablation of Ccr2 in aggrecan-expressing cells following knee injury ameliorates joint damage and pain during post-traumatic osteoarthritis.

H Willcockson, H Ozkan, L Arbeeva, E Mucahit, L Musawwir, L Longobardi

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Cartilage-SpecificBiomedicines · 2026
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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 at 1 institution in 1 country.

H WillcocksonDivision of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, NC, USA. Electronic address: helen_willcockson@med.unc.edu.
H OzkanDivision of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, NC, USA. Electronic address: ozkan@email.unc.edu.
L ArbeevaDivision of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, NC, USA. Electronic address: liubov_arbeeva@med.unc.edu.
E MucahitDivision of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, NC, USA. Electronic address: esranm@ad.unc.edu.
L MusawwirDivision of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, NC, USA. Electronic address: laylamus@ad.unc.edu.
L LongobardiDivision of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina-Chapel Hill, NC, USA. Electronic address: lara_longobardi@med.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

UNC Core Center for Clinical ResearchP30AR072580 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LEIGH Fleming CALLAHAN, Amanda E Nelson · 2019 to 2026
$6.1M
Role of CCR2 in osteoarthritisR01AR070821 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Lara Longobardi · 2017 to 2026
$3.1M
NIAMS NIH HHS P30 AR072580NIAMS NIH HHS R01 AR070821
6 · The paper itself

Abstract

objectiveTo investigate whether Ccr2 inactivation in aggrecan-expressing cells induced before post-traumatic OA (PTOA) onset or during progression, improves joint structures, synovial thickness and pain.

designWe induced a Ccr2 deletion in aggrecan-expressing cells (CCR2-AggKO) in skeletally mature mice using a tamoxifen-inducible Ccr2 inactivation. We stimulated PTOA changes (destabilization of medial meniscus, DMM) in CCR2-AggKO and CCR2+/+ mice, inducing recombination before DMM or 4 wks after DMM (early-vs late-inactivation). Joint damage was evaluated 2, 4, 8, 12 wks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous (incapacitance meter) and evoked pain (von-Frey filaments) were assessed up to 20 wks.

resultsEarly aggrecan-Ccr2 inactivation in CCR2-AggKO mice (N=8) resulted in improved ACS score (8-12wk, P=0.002), AC area (4-12wk, P<0.05) and Saf-O score (2wks P=0.004, 4wks P=0.02, 8-12wks P=0.002) compared to CCR2+/+. Increased subchondral bone thickness was delayed only at 2 wks and exclusively following early recombination. Osteophyte size was not affected, but osteophyte maturation (cartilage-to-bone) was delayed (4wks P=0.04; 8 wks P=0.03). Although late aggrecan-Ccr2 deletion led to some cartilage improvement, most data did not reach statistical significance; osteophyte maturity was delayed at 12wks. Early aggrecan-Ccr2 deletion led to improved pain measures of weight bearing compared to CCR2+/+ mice (N = 9, 12wks diff 0.13 [0.01, 0.26], 16wks diff 0.15 [0.05, 0.26], 20wks diff 0.23 [0.14, 0.31]). Improved mechanosensitivity in evoked pain, although less noticeable, was detected.

conclusionsWe demonstrated that deletion of Ccr2 in aggrecan expressing cells reduces the initiation but not progression of OA.

Indexed as

Cartilage, ArticularKnee InjuriesOsteoarthritisOsteophyteAggrecansAnimalsDisease Models, AnimalMicePainReceptors, CCR2AggrecansCcr2 protein, mouseReceptors, CCR2Animal modelBoneCartilageChemokinesJoint diseaseOsteoarthritis

Identifiers

PMID36075514
PMCPMC9671864
OpenAlexW4294723801

What OpenQuestion holds

Textmetadata
LicenceTDM
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.