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Updated: Jul 29, 2026
09:18
Isolation and Culture of Primary Synovial Macrophages and Fibroblasts from Murine Arthritis Tissue
Published on: February 24, 2023
TWEAK is a novel arthritogenic mediator.
Stuart J Perper1, Beth Browning, Linda C Burkly
1Exploratory Sciences, Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 5, 2006
Summary
Blocking TNF-like weak inducer of apoptosis (TWEAK) reduced rheumatoid arthritis severity in mice by decreasing joint inflammation and damage. TWEAK inhibition also impacted human cells, suggesting it as a potential therapeutic target for RA.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Rheumatoid arthritis (RA) is characterized by joint inflammation and destruction.
- Synovial fibroblasts in RA patients produce proinflammatory cytokines.
- TNF-like weak inducer of apoptosis (TWEAK) is implicated in inflammatory processes.
Purpose of the Study:
- To investigate the role of TWEAK in collagen-induced arthritis (CIA), a mouse model of RA.
- To evaluate the therapeutic potential of blocking TWEAK in RA.
- To explore the TWEAK/Fn14 pathway's involvement in human RA pathogenesis.
Main Methods:
- Administered neutralizing anti-TWEAK monoclonal antibody (mAb) in a mouse CIA model.
- Assessed clinical severity, joint inflammation, angiogenesis, and cartilage/bone erosion.
- Analyzed cellular and humoral responses, serum cytokine levels, and TWEAK's effect on human chondrocytes and osteoblasts in vitro.
Main Results:
- Serum TWEAK levels were elevated in CIA mice.
- Anti-TWEAK treatment significantly reduced CIA clinical severity and joint damage.
- TWEAK inhibition decreased pro-inflammatory mediators and matrix metalloproteinases.
- TWEAK induced matrix metalloproteinase production and inhibited chondrogenesis/osteogenesis in human cells.
Conclusions:
- TWEAK plays a significant role in RA pathogenesis by promoting inflammation, angiogenesis, and tissue damage.
- Blocking TWEAK is a promising therapeutic strategy for RA.
- The TWEAK/Fn14 pathway is a potential therapeutic target for human RA.
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