Molecular pathology of total knee arthroplasty instability defined by RNA-seq

• Published in: Genomics (San Diego, Calif.) Calif.), 2018-09, Vol.110 (5), p.247-256
• Main Authors: Lewallen, Eric A., Salib, Christopher G., Trousdale, William H., Berry, Charlotte E., Hanssen, Gabrielle M., Robin, Joseph X., Tibbo, Meagan E., Viste, Anthony, Reina, Nicolas, Morrey, Mark E., Sanchez-Sotelo, Joaquin, Hanssen, Arlen D., Berry, Daniel J., van Wijnen, Andre J., Abdel, Matthew P.
• Format: Article
• Language: English
• Subjects: Aged; Arthroplasty, Replacement, Knee - adverse effects; Case-Control Studies; Cell biology; collagen; extracellular matrix; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Female; Flexion instability; gene expression regulation; genes; Humans; Joint Instability - etiology; Joint Instability - genetics; Joint Instability - metabolism; Knee Joint - metabolism; Knee Joint - pathology; Knee Joint - surgery; knees; Male; Middle Aged; Molecular genetics; Oxidative Stress; pain; patients; Postoperative Complications - genetics; Postoperative Complications - metabolism; quantitative polymerase chain reaction; reverse transcriptase polymerase chain reaction; Revision total knee arthroplasty; risk factors; sequence analysis; Total knee arthroplasty; Transcriptome; transcriptomics
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2017.11.001

Total knee arthroplasty (TKA) is a durable and reliable procedure to alleviate pain and improve joint function. However, failures related to flexion instability sometimes occur. The goal of this study was to define biological differences between tissues from patients with and without flexion instability of the knee after TKA. Human knee joint capsule tissues were collected at the time of primary or revision TKAs and analyzed by RT-qPCR and RNA-seq, revealing novel patterns of differential gene expression between the two groups. Interestingly, genes related to collagen production and extracellular matrix (ECM) degradation were higher in samples from patients with flexion instability. Partitioned clustering analyses further emphasized differential gene expression patterns between sample types that may help guide clinical interpretations of this complication. Future efforts to disentangle the effects of physical and biological (e.g., transcriptomic modifications) risk factors will aid in further characterizing and avoiding flexion instability after TKA. •Flexion instability after total knee arthroplasty is examined using primary clinical tissues.•Gene expression levels are collected by RNA-seq and RT-qPCR.•High-throughput data and bioinformatics techniques are used to compare differentially expressed genes.•Genes related to extracellular matrix remodeling and oxidative stress are highlighted.•Possible future strategies to mitigate flexion instability after total knee arthroplasty are discussed.