Back to Search
Start Over
Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis.
- Source :
-
Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2024 Sep; Vol. 32 (9), pp. 1097-1112. Date of Electronic Publication: 2024 Mar 26. - Publication Year :
- 2024
-
Abstract
- Objective: Metabolic 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.<br />Design: We 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.<br />Results: Injured 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.<br />Conclusions: Acute 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.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Animals
Female
Male
Mice
Disease Models, Animal
Sex Factors
Synovial Membrane metabolism
Adipose Tissue metabolism
Inflammation Mediators metabolism
Receptors, Adrenergic, beta metabolism
Injections, Intra-Articular
Knee Injuries complications
Knee Injuries metabolism
Osteoarthritis, Knee metabolism
Osteoarthritis, Knee etiology
Cartilage, Articular metabolism
Cartilage, Articular drug effects
Cartilage, Articular pathology
Mice, Inbred C57BL
Isoproterenol pharmacology
Adrenergic beta-Agonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-9653
- Volume :
- 32
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Osteoarthritis and cartilage
- Publication Type :
- Academic Journal
- Accession number :
- 38527663
- Full Text :
- https://doi.org/10.1016/j.joca.2024.03.109