Host metalloproteinases in Lyme arthritis

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11407701&query_hl=1&itool=pubmed_docsum

Arthritis Rheum. 2001 Jun;44(6):1401-10.

Host metalloproteinases in Lyme arthritis.

Hu LT, Eskildsen MA, Masgala C, Steere AC, Arner EC, Pratta MA,
Grodzinsky AJ, Loening A, Perides G.

New England Medical Center, Boston, Massachusetts, USA.

OBJECTIVE: To assess the role of matrix metalloproteinases (MMPs)
in
cartilage and bone erosions in Lyme arthritis
METHODS: We examined synovial fluid from 10 patients with Lyme
arthritis for the presence of MMP-2, MMP-3, MMP-9, and "aggrecanase"
activity using gelatinolytic zymography and immunoblot analysis. We
developed an in vitro model of Lyme arthritis using cartilage explants
and observed changes in cartilage degradation in the presence of
Borrelia burgdorferi and/or various protease inhibitors.
RESULTS: Synovial fluid from patients with Lyme arthritis was found
to contain at least 3 MMPs: gelatinase A (MMP-2), stromelysin (MMP-3),
and gelatinase B (MMP-9). In addition, there was evidence in 2 patients

of "aggrecanase" activity not accounted for by the above enzymes.
Infection of cartilage explants with B. burgdorferi resulted in
induction of MMP-3, MMP-9, and "aggrecanase" activity. Increased
induction of these enzymes by B. burgdorferi alone was not sufficient
to
cause cartilage destruction in the explants as measured by
glycosaminoglycan (GAG) and hydroxyproline release. However, addition
of
plasminogen, which can act as an MMP activator, to cultures resulted in

significant GAG and hydroxyproline release in the presence of B.
burgdorferi. The MMP inhibitor batimastat significantly reduced the GAG

release and completely inhibited the collagen degradation.
CONCLUSION: MMPs are found in synovial fluids from patients with
Lyme
arthritis and are induced from cartilage tissue by the presence of B.
burgdorferi. Inhibition of MMP activity prevents B. burgdorferi-induced

cartilage degradation in vitro.

PMID: 11407701 [PubMed - indexed for MEDLINE]

.

Relevant Pages