Evidence map›Paper›PMID 26470720›Full record

ArticleAnnals of the rheumatic diseases2016

Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone.

Zhuang Cui, Janet Crane, Hui Xie, Xin Jin, Gehua Zhen, Changjun Li, Liang Xie, Long Wang, Qin Bian, Tao Qiu and 5 more

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

Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 2 pooled it
7.5field-weighted citation impact, top 2% 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

149 citing papers in PubMed, 2 syntheses or guidelines pooled it, 270 citations in OpenAlex.

  1. Pooled it
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  7. Programmed cell death in osteoarthritis.Apoptosis : an international journal on programmed cell death · 2026
    Review
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89 more citing papers are in PubMed but not listed here.

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

15 authors at 5 institutions in 2 countries.

Zhuang CuiDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Janet CraneDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Hui XieDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Xin JinDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Gehua ZhenDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Changjun LiDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Liang XieDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Long WangDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Qin BianDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Tao QiuDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Mei WanDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Min XieDepartment of Pharmaceutical Chemistry, Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California, USA.
Sheng DingDepartment of Pharmaceutical Chemistry, Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California, USA.
Bin YuDepartment of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Xu CaoDepartment of Orthopaedic Surgery, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Johns Hopkins Medicine · USJohns Hopkins University · USGladstone Institutes · USSouthern Medical University · CNUniversity of California, San Francisco · US

Funding

MECHANISM OF SMAD1 MEDIATED OSTEOBLAST DIFFERENTIATIONR01DK057501 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CAO, XU · 2001 to 2014
$3.8M
TGF-beta Activity in the Subchondral Bone and Onset of OAR01AR063943 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CAO, XU · 2013 to 2017
$2.2M
FUNCTION OF DNA VIRUS GENOMES IN ANIMAL CELLSZ01DK057501 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI OWENS, ROLAND ARVEL · 1986 to 2008
$846k
Temporal-spatial Regulation of MSCs by IGF-1K08AR064833 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CRANE, JANET · 2014 to 2018
$650k
Intramural NIH HHS Z01 DK057501NIAMS NIH HHS K08 AR064833NIAMS NIH HHS R01 AR063943NIDDK NIH HHS R01 DK057501
6 · The paper itself

Abstract

objectivesExamine whether osteoarthritis (OA) progression can be delayed by halofuginone in anterior cruciate ligament transection (ACLT) rodent models.

methods3-month-old male C57BL/6J (wild type; WT) mice and Lewis rats were randomised to sham-operated, ACLT-operated, treated with vehicle, or ACLT-operated, treated with halofuginone. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Immunostaining, flow cytometry, RT-PCR and western blot analyses were conducted to detect relative protein and RNA expression. Bone micro CT (μCT) and CT-based microangiography were quantitated to detect alterations of microarchitecture and vasculature in tibial subchondral bone.

resultsHalofuginone attenuated articular cartilage degeneration and subchondral bone deterioration, resulting in substantially lower OARSI scores. Specifically, we found that proteoglycan loss and calcification of articular cartilage were significantly decreased in halofuginone-treated ACLT rodents compared with vehicle-treated ACLT controls. Halofuginone reduced collagen X (Col X), matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS 5) and increased lubricin, collagen II and aggrecan. In parallel, halofuginone-attenuated uncoupled subchondral bone remodelling as defined by reduced subchondral bone tissue volume, lower trabecular pattern factor (Tb.pf) and increased thickness of subchondral bone plate compared with vehicle-treated ACLT controls. We found that halofuginone exerted protective effects in part by suppressing Th17-induced osteoclastic bone resorption, inhibiting Smad2/3-dependent TGF-β signalling to restore coupled bone remodelling and attenuating excessive angiogenesis in subchondral bone.

conclusionsHalofuginone attenuates OA progression by inhibition of subchondral bone TGF-β activity and aberrant angiogenesis as a potential preventive therapy for OA.

Indexed as

AnimalsAnterior Cruciate LigamentBone and BonesBone RemodelingBone ResorptionCartilage, ArticularDisease Models, AnimalDisease ProgressionMaleMiceMice, Inbred C57BLOsteoarthritisOsteoclastsPiperidinesQuinazolinonesRandom AllocationhalofuginonePiperidinesQuinazolinonesTransforming Growth Factor betaArthritisOsteoarthritisTreatment

Identifiers

PMID26470720
PMCPMC5013081
OpenAlexW2109118586

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.