Evidence map›Paper›PMID 38527663›Full record

ArticleOsteoarthritis and cartilage2024

Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis.

Ravi K Komaravolu, Padmaja Mehta-D'souza, Taylor Conner, Madeline Allen, Jessica Lumry, Albert Batushansky, Nathan P Pezant, Courtney G Montgomery, Timothy M Griffin

Open access · hybridAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Ravi K KomaravoluAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: ravikumar.komaravolu@gmail.com.
Padmaja Mehta-D'souzaAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: Padmaja-Mehta-Dsouza@omrf.org.
Taylor ConnerAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: Taylor-Conner@omrf.org.
Madeline AllenDepartment of Health and Exercise Science, University of Oklahoma, Norman, OK 73019, USA. Electronic address: madeline-allen@ouhsc.edu.
Jessica LumryAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: jessicalumry@gmail.com.
Albert BatushanskyAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: albert.batushansky@gmail.com.
Nathan P PezantCenter for Biomedical Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: Nathan-Pezant@omrf.org.
Courtney G MontgomeryCenter for Biomedical Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Genes and Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: Courtney-Montgomery@omrf.org.
Timothy M GriffinAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Oklahoma City VA Health Care System, Oklahoma City, OK 73104, USA; Oklahoma Center for Geroscience and the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: Tim-Griffin@omrf.org.
Oklahoma Medical Research Foundation · USUniversity of Oklahoma · US

Funding

Tracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI JUDITH A JAMES · 2013 to 2026
$68.2M
Autoimmune Drivers and Protectors Team Science (ADAPTS)U01AI176244 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES, Jeffrey C Rathmell · 2023 to 2026
$5.1M
Targeting Molecular Transducers of Exercise for Osteoarthritis TherapiesI01BX004666 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI GRIFFIN, TIMOTHY M · 2020 to 2023
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CMA: Cartilage Repair Strategies to Alleviate Arthritic Pain (CaRe AP): Optimizing the Host Environment for Intra-articular Osteoarthritis TherapiesI01BX004882 · VA · OKLAHOMA CITY VA MEDICAL CENTER · PI GRIFFIN, TIMOTHY M, JEFFRIES, MATLOCK · 2020 to 2025
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BLRD VA I01 BX004666BLRD VA I01 BX004882NIAID NIH HHS U01 AI176244NIGMS NIH HHS U54 GM104938
6 · The paper itself

Abstract

objectiveMetabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis (PTOA). Based on lipolytic and immunoregulatory actions of norepinephrine, we hypothesized that intra-articular β-adrenergic receptor (βAR) stimulation would suppress PTOA-associated inflammation in the infrapatellar fat pad (IFP) and synovium.

designWe used the βAR agonist isoproterenol to perturb intra-articular metabolism 3.5 weeks after applying a non-invasive single-load compression injury to knees of 12-week-old male and female mice. We examined the acute effects of intra-articular isoproterenol treatment relative to saline on IFP histology, multiplex gene expression of synovium-IFP tissue, synovial fluid metabolomics, and mechanical allodynia.

resultsInjured knees developed PTOA pathology characterized by heterotopic ossification, articular cartilage loss, and IFP atrophy and fibrosis. Isoproterenol suppressed the upregulation of pro-fibrotic genes and downregulated the expression of adipose genes and pro-inflammatory genes (Adam17, Cd14, Icam1, Csf1r, and Casp1) in injured joints of female (but not male) mice. Analysis of published single-cell RNA-seq data identified elevated catecholamine-associated gene expression in resident-like synovial-IFP macrophages after injury. Injury substantially altered synovial fluid metabolites by increasing amino acids, peptides, sphingolipids, phospholipids, bile acids, and dicarboxylic acids, but these changes were not appreciably altered by isoproterenol. Intra-articular injection of either isoproterenol or saline increased mechanical allodynia in female mice, whereas neither substance affected male mice.

conclusionsAcute βAR activation altered synovial-IFP transcription in a sex and injury-dependent manner, suggesting that women with PTOA may be more sensitive than men to treatments targeting sympathetic neural signaling pathways.

Indexed as

Adrenergic beta-AgonistsIsoproterenolAdipose TissueAnimalsCartilage, ArticularDisease Models, AnimalFemaleInflammation MediatorsInjections, Intra-ArticularKnee InjuriesMaleMiceMice, Inbred C57BLOsteoarthritis, KneeReceptors, Adrenergic, betaSex FactorsAdrenergic beta-AgonistsInflammation MediatorsIsoproterenolReceptors, Adrenergic, betaInfrapatellar fat padLipidsMetabolomicsSexual dimorphismSynovial fluid

Identifiers

PMID38527663
PMCPMC11330734
OpenAlexW4393189651

What Socratic 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 Socratic graph.