Evidence map›Paper›PMID 30485272›Full record

ArticlePloS one2018

Deficiency of the pattern-recognition receptor CD14 protects against joint pathology and functional decline in a murine model of osteoarthritis.

Nisha Sambamurthy, Cheng Zhou, Vu Nguyen, Ryan Smalley, Kurt D Hankenson, George R Dodge, Carla R Scanzello

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.0field-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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

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  16. Counteractive Effects of IL-33 and IL-37 on Inflammation in Osteoarthritis.International journal of environmental research and public health · 2022
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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

7 authors at 2 institutions in 1 country.

Nisha SambamurthyTranslational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.
Cheng ZhouTranslational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.
Vu NguyenTranslational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.
Ryan SmalleyTranslational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.
Kurt D HankensonDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan, United States of America.
George R DodgeTranslational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.
Carla R ScanzelloTranslational Musculoskeletal Research Center, Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-9290-188X
University of Pennsylvania · USUniversity of Michigan · US

Funding

Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)P30AR069619 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI LOUIS J SOSLOWSKY · 2016 to 2026
$9.1M
TRAINING PROGRAM/RHEUMATIC DISEASEST32AR007442 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BEHRENS, EDWARD M, MERKEL, PETER A · 1986 to 2018
$5.8M
The Toll-like receptor pathway in Meniscal Injury and OsteoarthritisK08AR057859 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI SCANZELLO, CARLA ROSE · 2010 to 2014
$620k
NIAMS NIH HHS K08 AR057859NIAMS NIH HHS P30 AR069619
6 · The paper itself

Abstract

objectiveCD14 is a monocyte/macrophage pattern-recognition receptor that modulates innate inflammatory signaling. Soluble CD14 levels in knee OA synovial fluids are associated with symptoms and progression of disease. Here we investigate the role of this receptor in development of OA using a murine joint injury model of disease.

methods10-week-old Male C57BL/6 (WT) and CD14-deficient (CD14-/-) mice underwent destabilization of the medial meniscus (DMM) surgery to induce OA. Joint histopathology was used to examine cartilage damage, and microCT to evaluate subchondral bone (SCB) remodeling at 6 and 19 weeks after surgery. Synovial and fat pad expression of macrophage markers (F4/80, CD11c, CD68, iNOS, CCR7, CD163 and CD206) was assessed by flow cytometry and droplet digital (dd)PCR. Changes in locomotive activity indicative of joint pain were evaluated longitudinally up to 16 weeks by automated behavioral analysis.

resultsEarly cartilage damage scores 6 weeks post-DMM were similar in both strains (Mean score ±SEM WT: 4.667±1.38, CD14-/-: 4.6±0.6), but at 19 weeks were less severe in CD14-/- (6.0±0.46) than in WT mice (13.44±2.5, p = 0.0002). CD14-/- mice were protected from both age-related and post-surgical changes in SCB mineral density and trabecular thickness. In addition, CD14-/- mice were protected from decreases in climbing activity (p = 0.015 vs. WT, 8 weeks) observed after DMM. Changes in synovial/fat pad expression of CCR7, a marker of M1 macrophages, were slightly reduced post-DMM in the absence of CD14, while expression of CD68 (pan-macrophage marker) and CD163 (M2 marker) were unchanged.

conclusionCD14 plays an important role in progression of structural and functional features of OA in the DMM model, and may provide a new target for therapeutic development.

Indexed as

AnimalsCartilageDisease Models, AnimalGene Expression RegulationJointsLipopolysaccharide ReceptorsMacrophagesMaleMenisci, TibialMice, Inbred C57BLOsteoarthritisReceptors, Pattern RecognitionRNA, MessengerX-Ray MicrotomographyLipopolysaccharide ReceptorsReceptors, Pattern RecognitionRNA, Messenger

Identifiers

PMID30485272
PMCPMC6261538
OpenAlexW2902726355

What OpenQuestion holds

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LicenceCC0
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.