PTOA: “Wide Range” of Potential Drug Candidates

A team from Lawrence Livermore National Laboratory (LLNL), University of California, Davis, University of California, Merced and Regeneron Pharmaceuticals are digging into post-traumatic osteoarthritis (PTOA).

As indicated in the May 19 news release, the scientists “examined the whole-joint gene expression by RNA sequencing at one day, one, six and 12 weeks after injury. The team used a new, non-invasive tibial compression mouse model of PTOA, that mimics ACL rupture in humans from a single high-impact injury.”

“The goal of the study was to see if there are biomarkers associated with cartilage degradation, which could then be further explored as therapeutic targets in future experiments, ” said Jiun Chang, a UC Merced graduate student mentored by LLNL’s Gaby Loots and the lead author of the study.

“This study provides the first account of gene expression changes associated with PTOA development and progression in this tibial compression model, ” said Aimy Sebastian, also a UC Merced graduate student mentored by Loots, who co-lead the study with Chang.

“By comparing our data to gene-expression data generated using the surgical destabilization of the medial meniscus PTOA model, we identified several common genes and shared mechanisms. Our study highlights several differences between these two models and suggests that the tibial compression model may be a more rapidly progressing model of PTOA, ” said Loots, an LLNL biologist who leads the team.

This study provides the first account of whole genome expression profiles to obtain new insights into the temporal progression of the disease.

Jiun Chang told OTW, “Our most interesting and surprising finding was the unveiling of a wide range of possible candidates to be tested as potential therapeutic targets. In addition, we were able to capture the molecular (RNA) changes over time with the progression of the disease in animal models, which collection of Human patient samples at early OA stages may present a change.

“Our transcriptional (RNA) data remains to be validated, therefore we have yet to understand which molecules contribute to OA and which molecules are ‘passengers, ’ meaning that their transcriptional changes do not contribute to the OA phenotype. Since OA is so complex, surgeons may find it surprising that patients with elevated levels of specific proteins in joints (post biopsy or joint replacements) may not necessarily be protected from OA. We may have to profile several proteins at the same time to be able to track the development of OA in people.”