CTRP3 exacerbates tendinopathy by dysregulating tendon stem cell differentiation and altering extracellular matrix composition

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Abstract

Neutralization of CTRP3 opposes degenerative tendon matrix remodeling during tendinopathy.

Abstract

Tendinopathy, the most common disorder affecting tendons, is characterized by chronic disorganization of the tendon matrix, which leads to tendon tear and rupture. The goal was to identify a rational molecular target whose blockade can serve as a potential therapeutic intervention for tendinopathy. We identified C1q/TNF-related protein-3 (CTRP3) as a markedly up-regulated cytokine in human and rodent tendinopathy. Overexpression of CTRP3 enhanced the progression of tendinopathy by accumulating cartilaginous proteoglycans and degenerating collagenous fibers in the mouse tendon, whereas CTRP3 knockdown suppressed the tendinopathy pathogenesis. Functional blockade of CTRP3 using a neutralizing antibody ameliorated overuse-induced tendinopathy of the Achilles and rotator cuff tendons. Mechanistically, CTRP3 elicited a transcriptomic pattern that stimulates abnormal differentiation of tendon stem/progenitor cells and ectopic chondrification as an effect linked to activation of Akt signaling. Collectively, we reveal an essential role for CTRP3 in tendinopathy and propose a potential therapeutic strategy for the treatment of tendinopathy.

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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

A. Subramanian, P. Tamayo, V. K. Mootha … (2005)

Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

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Causal analysis approaches in Ingenuity Pathway Analysis

John Osborne, Andreas Kramer, Jeff Green … (2015)

Motivation: Prior biological knowledge greatly facilitates the meaningful interpretation of gene-expression data. Causal networks constructed from individual relationships curated from the literature are particularly suited for this task, since they create mechanistic hypotheses that explain the expression changes observed in datasets. Results: We present and discuss a suite of algorithms and tools for inferring and scoring regulator networks upstream of gene-expression data based on a large-scale causal network derived from the Ingenuity Knowledge Base. We extend the method to predict downstream effects on biological functions and diseases and demonstrate the validity of our approach by applying it to example datasets. Availability: The causal analytics tools ‘Upstream Regulator Analysis', ‘Mechanistic Networks', ‘Causal Network Analysis' and ‘Downstream Effects Analysis' are implemented and available within Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com). Supplementary information: Supplementary material is available at Bioinformatics online.

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Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.

Mohit Kapoor, Johanne Martel-Pelletier, Daniel Lajeunesse … (2011)

Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed processes implicated in OA pathophysiology. Interleukin (IL)-1β and tumor necrosis factor (TNF), in particular, control the degeneration of articular cartilage matrix, which makes them prime targets for therapeutic strategies. Animal studies provide support for this approach, although only a few clinical studies have investigated the efficacy of blocking these proinflammatory cytokines in the treatment of OA. Apart from IL-1β and TNF, several other cytokines including IL-6, IL-15, IL-17, IL-18, IL-21, leukemia inhibitory factor and IL-8 (a chemokine) have also been shown to be implicated in OA and could possibly be targeted therapeutically. This Review discusses the current knowledge regarding the role of proinflammatory cytokines in the pathophysiology of OA and addresses the potential of anticytokine therapy in the treatment of this disease.

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Author and article information

Contributors

Yongsik Cho:

ORCID: https://orcid.org/0000-0002-4788-3141

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Hyeon-Seop Kim:

ORCID: https://orcid.org/0000-0003-3467-6626

Donghyun Kang:

ORCID: https://orcid.org/0000-0003-1966-1397

Role: ValidationRole: Writing - review & editing

Hyeonkyeong Kim:

ORCID: https://orcid.org/0000-0001-7190-8583

Role: ValidationRole: Writing - review & editing

Narae Lee: Role: ValidationRole: Writing - review & editing

Jihye Yun: Role: ValidationRole: Writing - review & editing

Yi-Jun Kim:

ORCID: https://orcid.org/0000-0002-1763-4267

Role: Writing - review & editing

Kyoung Min Lee:

ORCID: https://orcid.org/0000-0002-2372-7339

Role: ConceptualizationRole: Formal analysisRole: ResourcesRole: VisualizationRole: Writing - review & editing

Jin-Hee Kim: Role: Investigation

Hang-Rae Kim:

ORCID: https://orcid.org/0000-0002-3983-6193

Role: Resources

Young-il Hwang:

ORCID: https://orcid.org/0000-0002-5777-7983

Role: ConceptualizationRole: Data curationRole: SupervisionRole: Validation

Chris Hyunchul Jo:

ORCID: https://orcid.org/0000-0002-6161-5442

Role: ResourcesRole: Supervision

Jin-Hong Kim:

ORCID: https://orcid.org/0000-0002-6480-1929

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): sciadv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: November 2021

Publication date (Electronic, pub): 19 November 2021

Volume: 7

Issue: 47

Electronic Location Identifier: eabg6069

Affiliations

[1 ]Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea.

[2 ]Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea.

[3 ]School of Medicine, CHA University, 13496 Seongnam, South Korea.

[4 ]Institute of Convergence Medicine, Ewha Womans University Mokdong Hospital, 07985 Seoul, South Korea.

[5 ]Foot and Ankle Division, Department of Orthopedic Surgery, Seoul National University Bundang Hospital, 13620 Seongnam, South Korea.

[6 ]Department of Anatomy and Cell Biology, Seoul National University College of Medicine, 03080 Seoul, South Korea.

[7 ]Department of Orthopedic Surgery, Seoul Metropolitan Government–Seoul National University (SMG-SNU) Boramae Medical Center, Seoul National University College of Medicine, 07061 Seoul, South Korea.

[8 ]Interdisciplinary Program in Bioinformatics, Seoul National University, 08826 Seoul, South Korea.

Author notes

[* ]Corresponding author. Email: jinhkim@ 123456snu.ac.kr

[†]

These authors contributed equally to this work.

Author information

Yongsik Cho https://orcid.org/0000-0002-4788-3141

Hyeon-Seop Kim https://orcid.org/0000-0003-3467-6626

Donghyun Kang https://orcid.org/0000-0003-1966-1397

Hyeonkyeong Kim https://orcid.org/0000-0001-7190-8583

Yi-Jun Kim https://orcid.org/0000-0002-1763-4267

Kyoung Min Lee https://orcid.org/0000-0002-2372-7339

Hang-Rae Kim https://orcid.org/0000-0002-3983-6193

Young-il Hwang https://orcid.org/0000-0002-5777-7983

Chris Hyunchul Jo https://orcid.org/0000-0002-6161-5442

Jin-Hong Kim https://orcid.org/0000-0002-6480-1929

Article

Publisher ID: abg6069

DOI: 10.1126/sciadv.abg6069

PMC ID: 8604415

PubMed ID: 34797714

SO-VID: 87cc7376-ad77-4a63-8a67-4a0aaaa9cb9b

Copyright © Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 18 January 2021

Date accepted : 01 October 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003621, Ministry of Science, ICT and Future Planning;

Award ID: IBS-R008-D1