| Title: |
A CCL2/MCP-1 antagonist attenuates fibrosis of the infrapatellar fat pad in a rat model of arthritis |
| Authors: |
Hideya Yoshimura, Yusuke Nakagawa, Takeshi Muneta, Hideyuki Koga |
| Source: |
BMC Musculoskeletal Disorders, Vol 25, Iss 1, Pp 1-10 (2024) |
| Publisher Information: |
BMC, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Diseases of the musculoskeletal system |
| Subject Terms: |
Fibrosis, Infrapatellar fat pad, Osteoarthritis, CCL2, Macrophages, Gene therapy, Diseases of the musculoskeletal system, RC925-935 |
| More Details: |
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-β 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1471-2474 |
| Relation: |
https://doaj.org/toc/1471-2474 |
| DOI: |
10.1186/s12891-024-07737-y |
| Access URL: |
https://doaj.org/article/c2e076e7c2db4392b54bc0e26f96b068 |
| Accession Number: |
edsdoj.2e076e7c2db4392b54bc0e26f96b068 |
| Database: |
Directory of Open Access Journals |
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