Evidence map›Paper›PMID 24578232›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2014

Identification of α2-macroglobulin as a master inhibitor of cartilage-degrading factors that attenuates the progression of posttraumatic osteoarthritis.

Shaowei Wang, Xiaochun Wei, Jingming Zhou, Jing Zhang, Kai Li, Qian Chen, Richard Terek, Braden C Fleming, Mary B Goldring, Michael G Ehrlich and 2 more

2 registry-linked trialsOpen access · greenAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.3field-weighted citation impact, top 6% 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.

NCT03120988 phase1completednot on this mapstarted 2016, after this paper: background citation

Assessing Catabolic Marker Levels in the Knee Synovial Fluid Microenvironment After Lavage With Platelet Poor Plasma (PPP)

TypeinterventionalSponsorRegenexx, LLCRan2016 to 2017Enrolled10ConditionsKnee OsteoarthritisArmsLavage with Platelet Poor Plasma (PPP)
NCT04066933 unknown statusnot on this mapstarted 2018, after this paper: background citation

Neurogenic Thoracic Outlet Syndrome and Other Forms of Cervical Brachial Syndrome Treated With Plasma Concentrate Enriched for Alpha 2 Macroglobulin

TypeobservationalSponsorNeurological Associates of West Los AngelesRan2018 to 2023Enrolled60ConditionsComplex Regional Pain Syndromes, Neuralgia, Thoracic Outlet Neurologic SyndromeArmsA2M enriched plasma
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 89 citations in OpenAlex.

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  12. Current and Emerging Biologic Therapies for Equine Tendon and Ligament Injuries.The Veterinary clinics of North America. Equine practice · 2025
    Review
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  16. Orthobiologics in knee osteoarthritis, dream or reality?Archives of orthopaedic and trauma surgery · 2024
    Review
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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

12 authors at 6 institutions in 3 countries.

Shaowei WangWarren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island; The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China, and Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Xiaochun Wei
Jingming Zhou
Jing Zhang
Kai Li
Qian Chen
Richard Terek
Braden C Fleming
Mary B Goldring
Michael G Ehrlich
Ge Zhang
Lei Wei
Brown University · USRhode Island Hospital · USHong Kong Baptist University · HKHospital for Special Surgery · USSecond Hospital of Shanxi Medical University · CNShanxi Medical University · CN

Funding

RI COBRE: REGULATION OF GROWTH PLATE DEVELOPMENT BYNUCLEAR/CYTOPLASMIC FACTORSP20RR024484 · NCRR · RHODE ISLAND HOSPITAL · PI TEREK, RICHARD M · 2007 to 2011
$11.9M
COBRE for Skeletal Health and RepairP20GM104937 · NIGMS · RHODE ISLAND HOSPITAL · PI CHEN, QIAN · 2012 to 2016
$10.8M
Histone Deacetylation Regulates Growth Plate DevelopmentR01AR059142 · NIAMS · RHODE ISLAND HOSPITAL · PI WEI, LEI · 2011 to 2015
$1.5M
Targeting CXCR4 and microRNA as Therapy for ChondrosarcomaR01CA166089 · NCI · RHODE ISLAND HOSPITAL · PI TEREK, RICHARD M · 2013 to 2017
$1.4M
NCI NIH HHS R01 CA166089NCI NIH HHS R01-CA-166089NCRR NIH HHS P20 RR024484NCRR NIH HHS P20-RR-024484NIAMS NIH HHS R01 AR059142NIAMS NIH HHS R01-AR-059142NIGMS NIH HHS P20 GM104937
6 · The paper itself

Abstract

objectiveTo determine if supplemental intraarticular α2-macroglobulin (α2 M) has a chondroprotective effect in a rat model of osteoarthritis (OA).

methodsUsing Western blotting, mass spectrometry, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry, α2 M was identified as a potential therapeutic agent through a comparison of α2 M concentrations in serum, synovial fluid (SF), and cartilage from normal subjects and patients with OA. In cultured chondrocytes, the effects of α2 M on interleukin-1 (IL-1)-induced cartilage catabolic enzymes were evaluated by Luminex assay and ELISA. In vivo effects on cartilage degeneration and matrix metalloproteinase 13 (MMP-13) concentration were evaluated in male rats (n = 120) randomized to 1 of 4 treatments: 1) anterior cruciate ligament transection (ACLT) and saline injections, 2) ACLT and 1 IU/kg injections of α2 M, 3) ACLT and 2 IU/kg injections of α2 M, or 4) sham operation and saline injections. Rats were administered intraarticular injections for 6 weeks. The concentration of MMP-13 in SF lavage fluid was measured using ELISA. OA-related gene expression was quantified by real-time quantitative polymerase chain reaction. The extent of OA progression was graded by histologic examination.

resultsIn both normal subjects and OA patients, α2 M levels were lower in SF as compared to serum, and in OA patients, MMP-13 levels were higher in SF than in serum. In vitro, α2 M inhibited the induction of MMP-13 by IL-1 in a dose-dependent manner in human chondrocytes. In the rat model of ACLT OA, supplemental intraarticular injection of α2 M reduced the concentration of MMP-13 in SF, had a favorable effect on OA-related gene expression, and attenuated OA progression.

conclusionThe plasma protease inhibitor α2 M is not present in sufficient concentrations to inactivate the high concentrations of catabolic factors found in OA SF. Our findings suggest that supplemental intraarticular α2 M provides chondral protection in posttraumatic OA.

Indexed as

Agedalpha-MacroglobulinsAnimalsAnterior Cruciate LigamentAnterior Cruciate Ligament InjuriesCartilageChondrocytesDisease Models, AnimalDisease ProgressionFemaleHumansInjections, Intra-ArticularKnee InjuriesMaleMatrix Metalloproteinase 13Middle Agedalpha-MacroglobulinsMatrix Metalloproteinase 13MMP13 protein, humanMmp13 protein, rat

Identifiers

PMID24578232
PMCPMC4187342
OpenAlexW1534343003

What OpenQuestion holds

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Registered trials

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.