Journal article
Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury
Osteoarthritis and cartilage, v 32(10), pp 1295-1307
Oct 2024
PMID: 39004209
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis.
Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n = 10/group) and micromechanical testing (n = 5/group) to identify changes in tissue architecture and stiffness. Additional samples (n = 5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n = 6 (IL1) or n = 8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6).
Cruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators.
Spontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.
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Details
- Title
- Interleukin receptor therapeutics attenuate inflammation in canine synovium following cruciate ligament injury
- Creators
- Elisabeth A. Lemmon - University of PennsylvaniaKevin G. Burt - University of PennsylvaniaSung Yeon Kim - University of PennsylvaniaBryan Kwok - Drexel University, School of Biomedical Engineering, Science, and Health SystemsLorielle Laforest - University of PennsylvaniaRui Xiao - University of PennsylvaniaLin Han - Drexel University, School of Biomedical Engineering, Science, and Health SystemsCarla R. Scanzello - University of PennsylvaniaRobert L. Mauck - University of PennsylvaniaKimberly A. Agnello - University of Pennsylvania
- Publication Details
- Osteoarthritis and cartilage, v 32(10), pp 1295-1307
- Publisher
- Elsevier
- Number of pages
- 13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001317318300001
- Scopus ID
- 2-s2.0-85200210233
- Other Identifier
- 991021893681604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Orthopedics
- Rheumatology