Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.

ABSTRACT:

Objective

The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA-DRB1-coded 5-amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)-mediated bone damage in collagen-induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis-associated bone damage, we sought to determine the therapeutic targetability of calreticulin.

Methods

A library of backbone-cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE-activated signaling and OC differentiation was test

SUBMITTER: Ling S 

PROVIDER: S-EPMC4784479 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature