An Herbal Derivative as the Basis for a New Approach to Treating Post-Traumatic Osteoarthritis
Abstract
Osteoarthritis (OA) is a painful disease that causes the progressive destruction of joint structures, and is the most common cause of disability among military service members who are removed from active duty for medical reasons. In preliminary work with a small number of animals, we have found that the natural product derivative halofuginone (HF) shows promise with respect to reducing cartilage damage in the destabilized medial meniscus (DMM) mouse model of PTOA. HF inhibits glutamyl- prolyl-tRNA synthetase (EPRS), the enzyme responsible for charging tRNAs with the amino acid proline. The goal of this grant is to test the hypothesis that EPRS inhibitors will provide the basis for a new therapeutic strategy for PTOA. We report here: 1) Preliminary analysis of a study of efficacy of the EPRS inhibitors HF and its less toxic derivative HFol, on PTOA in mice, using the DMM model; 2) Data examining the transcriptomics of HF effects on responses to cytokines in synoviocytes. 3) preliminary characterization of an in vitro chondrocyte system in which chondrocytes retain strong responsiveness to cytokines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2018
- Accession Number
- AD1093547
Entities
People
- Yefu Li
Organizations
- Harvard College