Host metalloproteinases in Lyme arthritis

Area of Science:

• Biochemistry
• Immunology
• Rheumatology

Background:

• Lyme arthritis is characterized by joint inflammation and potential cartilage and bone erosion.
• Matrix metalloproteinases (MMPs) are implicated in the degradation of extracellular matrix components in arthritic conditions.

Purpose of the Study:

• To investigate the role of specific MMPs in the pathogenesis of cartilage and bone erosions in Lyme arthritis.
• To determine if Borrelia burgdorferi directly induces MMPs and subsequent cartilage degradation.

Main Methods:

• Synovial fluid analysis from Lyme arthritis patients for MMP-2, MMP-3, MMP-9, and aggrecanase activity.
• In vitro model using cartilage explants infected with Borrelia burgdorferi, with and without protease inhibitors and plasminogen.

Main Results:

• Synovial fluid contained MMP-2, MMP-3, and MMP-9; aggrecanase activity was also detected.
• Borrelia burgdorferi infection induced MMP-3, MMP-9, and aggrecanase activity in cartilage explants.
• Cartilage degradation (GAG and hydroxyproline release) occurred when plasminogen was added, and was significantly reduced by MMP inhibition (batimastat).

Conclusions:

• MMPs are present in Lyme arthritis synovial fluid and are upregulated by Borrelia burgdorferi in cartilage.
• MMP activity inhibition effectively prevents Borrelia burgdorferi-induced cartilage degradation in an in vitro model.