An Herbal Derivative as the Basis for a New Approach to Treating Post-Traumatic Osteoarthritis
Technical Report,01 Sep 2015,31 Aug 2018
Harvard College, President and Fellows of Sponsored Programs Boston United States
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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.
- Medicine and Medical Research