Inhibiting the expression of GPR43 in macrophages can alleviate osteoarthritis by suppressing the M1 polarization and
Haokun Mo1, Yanjun Hou1, Junchen He1
1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Abstract:
G-protein-coupled receptor 43 (GPR43) plays an important role in immunomodulation, metabolic regulation and ROS production. Our research aims to explore the role and mechanism of GPR43 in osteoarthritis (OA). We experimentally determined that following the intervention of macrophages with lipopolysaccharide (LPS), there is a significant upregulation in the expression of GPR43. GPR43 knockdown in macrophages can inhibit the M1 polarization and reactive oxygen species (ROS) production. Meanwhile, GPR43 knockdown can alleviate osteoarthritis in destabilized medial meniscus (DMM) induced OA mouse models. In mechanism, GPR43 knockdown in macrophages can inhibit the expression of CX3C chemokine ligand 1 (CX3CL1) and the activation of NF-κB signaling pathway, thereby exerting a therapeutic effect on OA. Overall, knockdown of GPR43 in macrophages can alleviate OA by inhibiting M1 polarization and ROS production via the CX3CL1/NF-κB signaling pathway. GPR43 is a potential therapeutic target for OA.
Insights
Knocking down G-protein-coupled receptor 43 (GPR43) in macrophages reduces inflammation and oxidative stress, alleviating osteoarthritis. This suggests GPR43 is a potential therapeutic target for treating osteoarthritis.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- G-protein-coupled receptor 43 (GPR43) is implicated in immune responses, metabolism, and reactive oxygen species (ROS) generation.
- Osteoarthritis (OA) is a degenerative joint disease with significant inflammatory components.
Purpose of the Study:
- To investigate the role and underlying mechanisms of GPR43 in the pathogenesis of osteoarthritis.
- To evaluate GPR43 as a potential therapeutic target for OA treatment.
Main Methods:
- Macrophages were stimulated with lipopolysaccharide (LPS) to assess GPR43 expression.
- GPR43 knockdown was performed in macrophages and in a destabilized medial meniscus (DMM) induced mouse model of OA.
- Key signaling pathways, including NF-κB, and molecular markers of inflammation (M1 polarization) and oxidative stress (ROS) were analyzed.
Main Results:
- LPS stimulation led to significant upregulation of GPR43 expression in macrophages.
- GPR43 knockdown inhibited M1 polarization and reduced ROS production in macrophages.
- GPR43 knockdown ameliorated OA symptoms in the DMM mouse model.
- Mechanistically, GPR43 knockdown suppressed CX3C chemokine ligand 1 (CX3CL1) expression and NF-κB pathway activation.
Conclusions:
- GPR43 plays a critical role in promoting M1 polarization and ROS production in macrophages during OA.
- Targeting GPR43 in macrophages alleviates OA by modulating the CX3CL1/NF-κB signaling pathway.
- GPR43 represents a promising therapeutic target for osteoarthritis intervention.
