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Transcriptomic analysis of synovial extracellular RNA following knee trauma: A pilot study
Authors:Anthony J. Griswold  Jose Perez  Karen Nuytemans  Thomas A. Strong  Liyong Wang  Danica D. Vance  Hayley Ennis  Marvin K. Smith  Thomas M. Best  Jeffery M. Vance  Margaret A. Pericak‐Vance  Lee D. Kaplan
Affiliation:1. UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, Florida;2. John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida;3. Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School Medicine, University of Miami, Miami, Florida;4. Department of Orthopaedic Surgery, Columbia University Medical Center, New York, New York;5. Departments of Orthopedics, Biomedical Engineering, Kinesiology, Miller School Medicine, University of Miami, Miami, Florida
Abstract:
Traumatic knee injuries often result in damage to articular cartilage and other joint structures. Such trauma is a strong risk factor for the future development and progression of osteoarthritis (OA). The molecular mechanisms and signaling pathways modulating response to knee joint trauma remain unclear. Moreover, investigations of biomarkers influencing responses have been targeted rather than broad, unbiased discovery studies. Herein, we characterize the complete complement of extracellular RNA (exRNA) in the synovial fluid of 14 subjects following knee injury. Fluid was collected during surgery from the injured knees, and from the contralateral knee in a subset, undergoing surgical repair of the ACL and/or meniscal repair/debridement. Arthroscopic grading of chondral damage in four knee compartments was performed using the Outerbridge classification. exRNA was extracted and subjected to massively parallel total RNA sequencing. Differential abundance of RNA was calculated between the subject cohorts of injured and non‐injured knee, average Outerbridge score ≥0.5 and less, and chronic and acute injury duration defined as ≤4 months till surgery or longer. Overall, expression of several thousand genes was identified in the synovial fluid. Furthermore, differential expression analysis suggests a role of exRNA fragments of matrix metalloproteinases and skeletal muscle fiber genes in the response to traumatic injury. Together, these data suggest that high‐throughput approaches can indicate exRNA molecular signatures following knee trauma. Future studies are required to more fully characterize the biological roles of these exRNA and the cadence of their respective release that may lead to translational treatment options for post‐traumatic OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1659–1665, 2018.
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