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AMPA/kainate glutamate receptor antagonists prevent posttraumatic osteoarthritis
Cleo S Bonnet1,2, Sophie J Gilbert1,2, Emma J Blain1,2
1School of Biosciences.
JCI Insight
|June 17, 2020
Summary
Glutamate receptor antagonists show promise in preventing osteoarthritis after joint injury. In a mouse model, NBQX significantly reduced swelling and degeneration, outperforming current treatments and offering a new therapeutic avenue.
Area of Science:
- Orthopedics
- Neuroscience
- Pharmacology
Background:
- Musculoskeletal disorders, particularly osteoarthritis, impose a significant global health burden.
- Osteoarthritis is a leading cause of chronic pain, affecting millions worldwide, with limited treatment options for joint degeneration.
- Joint injury can trigger glutamate release, leading to pain, inflammation, and degeneration within the joint.
Purpose of the Study:
- To investigate glutamate concentrations and glutamate receptor (GluR) expression in human injured joints.
- To compare the efficacy of GluR antagonists with current treatments in preventing injury-induced osteoarthritis using a mouse model.
Main Methods:
- Analysis of synovial fluid glutamate levels and GluR expression in human injured joints.
- Utilizing a mouse model of anterior cruciate ligament (ACL) rupture to induce osteoarthritis.
- Administering intra-articular injections of NBQX (a GluR antagonist), hyaluronic acid (HA), or Depo-Medrone at the time of injury.
Main Results:
- GluRs were found in ligaments and meniscus post-knee injury; synovial fluid glutamate ranged from 19 to 129 microM.
- NBQX administration significantly reduced swelling and degeneration in the mouse osteoarthritis model.
- Hyaluronic acid showed no effect, while Depo-Medrone provided short-term swelling reduction but increased degeneration.
Conclusions:
- Intra-articular NBQX demonstrated superior efficacy in mitigating symptoms and disease progression compared to current treatments.
- Repurposing existing drugs targeting glutamate receptors, developed for CNS disorders, could offer a novel strategy for preventing post-traumatic osteoarthritis.
- This approach holds potential for rapidly reducing the substantial burden of osteoarthritis.
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