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New research could help prevent arthritis after ACL injury

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About half of all people who rupture the anterior cruciate ligament (ACL) in their knee will go on to develop post-traumatic osteoarthritis (PTOA) within 10 to 20 years of the injury.

But if we can better understand the molecular and cellular mechanisms that lead to the knee cartilage degenerating, it might be possible to develop new treatments that could be administered immediately after injury to prevent the development of PTOA years later.

Researchers at Lawrence Livermore National Laboratory recently examined the whole-joint gene expression by RNA sequencing at one day and one, six and 12 weeks after injury. The team, working with colleagues from the University of California, Davis; University of California, Merced; and Regeneron Pharmaceuticals, used a new, non-invasive tibial compression mouse model of PTOA that mimics ACL rupture in humans from a single high-impact injury.

In a study published in the online edition of the Journal of Orthopaedic Research, the scientists report that they identified 1,446 genes differentially expressed in injured joints, including several known regulators of osteoarthritis, as well as many new genes. They also identified 18 long, non-coding RNAs differentially expressed in the injured joints, RNAs that have not yet been explored functionally in this context.

Identifying and characterising osteoarthritis biomarkers for detecting and tracking the progression of the disease, combined with the development of new pharmacologic interventions to minimise cartilage damage, could personalise medical treatment before the disease is all consuming, Lawrence Livermore National Laboratory said.

“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,” explained 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,” added Aimy Sebastian, also a UC Merced graduate student mentored by Loots, who co-led the study with Chang.

Chang explains the research in more detail in a YouTube video at https://youtu.be/ypkUFSPz5fY.