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Host metalloproteinases in Lyme arthritis

L T Hu1, M A Eskildsen, C Masgala

  • 1New England Medical Center, Boston, Massachusetts, USA.

Arthritis and Rheumatism
|June 16, 2001
PubMed
Abstract

Insights

Matrix metalloproteinases (MMPs) are present in Lyme arthritis synovial fluid and induced by Borrelia burgdorferi. Inhibiting MMPs prevents cartilage damage in this Lyme arthritis model.

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.

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