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Published on: May 31, 2018
Controlled release of CD200 inhibits inflammatory macrophages and chondrocyte catabolism
Shreedevi Kumar1, Folly M Patterson1,2, Tiffany Conklin1
1J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
Abstract:
In the osteoarthritic joint, activated macrophages release pro-inflammatory factors that promote cartilage degeneration. The CD200:CD200R immune checkpoint pathway is a promising therapeutic target that inhibits classical macrophage activation. We hypothesized that the presentation of CD200 to macrophages would shift their cytokine profile from pro-inflammatory to pro-regenerative, thereby reducing chondrocyte catabolism. CD200 encapsulated in poly(lactide-co-glycolide) microparticles (MPs) were incubated with murine bone marrow-derived macrophages. CD200 MP treatment reduced protein and gene expression of pro-inflammatory mediators in M1 macrophages and increased protein and gene expression of anti-inflammatory mediators in M2 and M1/2 macrophages. Conditioned media from CD200 MP-treated M1 macrophages reduced the expression of catabolic enzyme genes in chondrocytes. This study is the first to demonstrate that delivery of CD200 alters the inflammatory cascade and paracrine signaling to chondrocytes. There is significant potential for the CD200:CD200R inhibitory signaling pathway to be leveraged as an intra-articular treatment of OA.
Insights
Delivering CD200 via microparticles shifts macrophages to a regenerative state, reducing cartilage breakdown in osteoarthritis. This approach shows promise for intra-articular OA treatment.
Area of Science:
- Immunology
- Biomaterials Science
- Orthopedics
Background:
- Osteoarthritis (OA) involves pro-inflammatory macrophages driving cartilage degeneration.
- The CD200:CD200R pathway regulates macrophage activation and is a potential therapeutic target.
Purpose of the Study:
- To investigate if CD200 delivery to macrophages can alter their inflammatory profile towards regeneration.
- To assess the impact of CD200 on chondrocyte catabolism in an OA context.
Main Methods:
- CD200 protein was encapsulated in poly(lactide-co-glycolide) microparticles (MPs).
- Murine bone marrow-derived macrophages were treated with CD200-loaded MPs.
- Gene and protein expression of inflammatory and anti-inflammatory mediators were analyzed.
- Chondrocytes were exposed to conditioned media from treated macrophages.
Main Results:
- CD200 MP treatment decreased pro-inflammatory mediators (M1) and increased anti-inflammatory mediators (M2/M1/2).
- Conditioned media from CD200 MP-treated M1 macrophages reduced chondrocyte expression of catabolic enzyme genes.
- This study demonstrates CD200 delivery alters macrophage inflammatory cascades and paracrine signaling.
Conclusions:
- CD200 delivery via microparticles effectively modulates macrophage phenotype from pro-inflammatory to pro-regenerative.
- This strategy shows potential for reducing chondrocyte catabolism and offers a novel intra-articular treatment for osteoarthritis.
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