A CCL2/MCP-1 antagonist attenuates fibrosis of the infrapatellar fat pad in a rat model of arthritis.
BMC Musculoskelet Disord
; 25(1): 674, 2024 Aug 29.
Article
em En
| MEDLINE
| ID: mdl-39210303
ABSTRACT
BACKGROUND:
Fibrosis of the infrapatellar fat pad (IFP) is a feature of osteoarthritis and contributes substantially to the pain and dysfunction in patients' joints. However, the underlying mechanisms remain unclear. C-C motif chemokine ligand-2 (CCL2) plays a central role in tissue fibrosis. Thus, we aimed to investigate the role of CCL2 in the development of IFP fibrosis in a rat model of arthritis, hypothesizing that a CCL2 antagonist could mitigate fibrotic progression.METHODS:
We induced arthritis in male Wistar rats using intra-articular injections of carrageenan. Furthermore, to evaluate the effects of a CCL2 antagonist on protein expression and collagen deposition in the IFP of the rats, we transferred an N-terminal-truncated CCL2 gene into a rat model via electroporation-mediated intramuscular injection. Macrophage infiltration and collagen deposition in the IFP were analyzed in vivo. Groups were compared using the Mann-Whitney U test and Student's t-test.RESULTS:
We identified infiltrating macrophages as well as increases in CCL2 and TGF-ß levels as collagen deposition progressed. Gene transfer of the CCL2-antagonist before arthritis induction attenuated collagen deposition remarkably.CONCLUSIONS:
We provide initial evidence that anti-CCL2 gene therapy can effectively suppress the development of IFP fibrosis in a rat model. Thus, targeting CCL2 holds promise as a therapeutic strategy for managing tissue fibrosis in osteoarthritis patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Fibrose
/
Tecido Adiposo
/
Ratos Wistar
/
Quimiocina CCL2
Limite:
Animals
Idioma:
En
Revista:
BMC Musculoskelet Disord
Ano de publicação:
2024
Tipo de documento:
Article