Transcriptomic analysis of synovial extracellular RNA following knee trauma: A pilot study

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.

Synovial Fluid Cytokine Profile at the Time of Arthroscopy Explains Intermediate-Term Functional Outcomes

“…11,16 Levels of MMP-3 are known to increase as a result of abnormal cartilage loading or acute injury to the menisci or ligamentous structures, and studies have found that MMP-3 is associated with greater cartilage loss and pain. 10,19,21,24,35 The aforementioned studies also found that although levels of other biomarkers decrease after the acute phase of injury, MMP-3 remains elevated. These findings alongside numerous studies implicating MMP-3 as a modulator of nociception may explain its association with long-term pain scores.…”

Prolidase expression in knee osteoarthritis and healthy controls

“…The measurement of enzymatic activity in serum will allow us to know if the decrease in the expression of the protein in the tissue in an early event is a consequence of the inflammatory alteration or by the damage of the synovial membrane. [ 25 , 26 , 27 ] This information would serve to assess the damage caused by the progression of KOA.…”

Pain Characteristics and Biomarkers in Treatment Approaches for Osteoarthritis Pain

“…However, clinical trials using subgroup analyses based on clinical features and/or biomarkers will still be needed to confirm the efficacy of specific drugs in patients with these characteristics [118]. Finally, work examining biomarkers for OA risk factors, such as biomarkers linking obesity and OA [119,120] or markers that might elucidate connections between OA and aging [121] or knee injury [122,123], could support clinical guidance for the treatment of OA in specific patient subgroups.…”