Evidence map›Paper›PMID 29436471›Full record

ArticleAnnals of the rheumatic diseases2018

Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair.

Ruzanna Shkhyan, Ben Van Handel, Jacob Bogdanov, Siyoung Lee, Yifan Yu, Mila Scheinberg, Nicholas W Banks, Sean Limfat, Arthur Chernostrik, Carlos Eduardo Franciozi and 12 more

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

Article in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

35 citing papers in PubMed, 58 citations in OpenAlex.

  1. [Advances in immunomodulatory strategies for meniscal regeneration].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
    Review
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  7. The Mechanism by WhichJournal of inflammation research · 2024
    Article
  8. FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
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  17. Advances in Regenerative Sports Medicine Research.Frontiers in bioengineering and biotechnology · 2022
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 3 countries.

Ruzanna Shkhyan *Department of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Ben Van Handel *Department of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Jacob Bogdanov *Department of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Siyoung LeeDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Yifan YuDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Mila ScheinbergDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Nicholas W BanksDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Sean LimfatDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Arthur ChernostrikDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Carlos Eduardo FrancioziDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Mohammad Parvez AlamDrug Discovery Laboratory, Department of Neurology, University of California at Los Angeles, Los Angeles, California, USA.
Varghese JohnDrug Discovery Laboratory, Department of Neurology, University of California at Los Angeles, Los Angeles, California, USA.
Ling WuDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Gabriel B FergusonDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Ali NsairDepartment of Medicine, Division of Cardiology, David Geffen School of Medicine (DGSOM), University of California, Los Angeles, California, USA.
Frank A PetriglianoDepartment of Orthopaedic Surgery, David Geffen School of Medicine (DGSOM), University of California at Los Angeles, Los Angeles, California, USA.
C Thomas VangsnessDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Kanagasabai VadivelDepartment of Orthopaedic Surgery, David Geffen School of Medicine (DGSOM), University of California at Los Angeles, Los Angeles, California, USA.
Paul BajajDepartment of Orthopaedic Surgery, David Geffen School of Medicine (DGSOM), University of California at Los Angeles, Los Angeles, California, USA.
Liming WangDepartment of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Nancy Q LiuDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
Denis EvseenkoDepartment of Orthopaedic Surgery, University of Southern California (USC), Los Angeles, California, USA.
University of Southern California · USUniversity of California, Los Angeles · USNanjing Medical University · CNUniversidade Federal de São Paulo · BR

Funding

GP130/STAT3 signalling in articular cartilage development and regenerationR01AR071734 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EVSEENKO, DENIS, LYONS, KAREN M. · 2018 to 2022
$3.0M
Dissecting molecular mechanisms implicated in age- and osteoarthritis-related decline in anabolism in articular cartilageR01AG058624 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EVSEENKO, DENIS · 2019 to 2023
$1.7M
Generation of human chondroprogenitor cells for cartilage restorationK01AR061415 · NIAMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EVSEENKO, DENIS · 2011 to 2015
$581k
NIAMS NIH HHS K01 AR061415NIAMS NIH HHS R01 AR071734NIA NIH HHS R01 AG058624
6 · The paper itself

Abstract

objectiveHuman adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs.

methodsHigh throughput screening of 170 000 compounds identified a small molecule gp130 modulator termed regulator of cartilage growth and differentiation (RCGD 423) that promotes atypical homodimeric signalling in the absence of cytokine ligands, driving transient increases in MYC and pSTAT3 while suppressing oncostatin M- and IL-6-mediated activation of ERK and NF-κB via direct competition for gp130 occupancy.

resultsThis small molecule increased proliferation while reducing apoptosis and hypertrophic responses in adult chondrocytes in vitro. In a rat partial meniscectomy model, RCGD 423 greatly reduced chondrocyte hypertrophy, loss and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Moreover, RCGD 423 improved cartilage healing in a rat full-thickness osteochondral defect model, increasing proliferation of mesenchymal cells in the defect and also inhibiting breakdown of cartilage matrix in de novo generated cartilage.

conclusionThese results identify a novel strategy for AC remediation via small molecule-mediated modulation of gp130 signalling.

Indexed as

AnimalsCartilage, ArticularCartilage DiseasesCell ProliferationChondrocytesCytokine Receptor gp130Disease Models, AnimalGenes, mycRatsSignal TransductionSTAT3 Transcription FactorCytokine Receptor gp130Stat3 protein, ratSTAT3 Transcription Factorarthritischondrocytesdisease activityDMARDsinflammation

Identifiers

PMID29436471
PMCPMC8444286
OpenAlexW2787618482

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.