Molecular pathology of adverse local tissue reaction caused by metal-on-metal implants defined by RNA-seq

• Published in: Genomics (San Diego, Calif.) Vol. 111; no. 6; pp. 1404 - 1411
• Main Authors: Salib, Christopher G., Lewallen, Eric A., Paradise, Christopher R., Tibbo, Meagan E., Robin, Joseph X., Trousdale, William H., Morrey, Logan M., Xiao, Jason, Turner, Travis W., Limberg, Afton K., Jay, Anthony G., Thaler, Roman, Dudakovic, Amel, Sanchez-Sotelo, Joaquin, Morrey, Mark E., Berry, Daniel J., Lewallen, David G., van Wijnen, Andre J., Abdel, Matthew P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2019
• Subjects: Adverse local tissue reaction; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip - adverse effects; Case-Control Studies; Cell biology; Female; Foreign-Body Reaction - etiology; Foreign-Body Reaction - metabolism; Foreign-Body Reaction - pathology; High-Throughput Nucleotide Sequencing; Humans; Male; Metal-on-metal; Metal-on-Metal Joint Prostheses - adverse effects; Metallosis; Middle Aged; Molecular genetics; Osteoarthritis - pathology; Osteoarthritis - surgery; Pathology, Molecular; Prosthesis Failure - etiology; Reoperation; Synoviocytes - metabolism; Synoviocytes - pathology; Total hip arthroplasty; Transcriptome; Cell biology; Adverse local tissue reaction; Molecular genetics; Metal-on-metal; Total hip arthroplasty; Metallosis
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2018.09.013

Total hip arthroplasty (THA) alleviates hip pain and improves joint function. Current implant design permits long-term survivorship of THAs, but certain metal-on-metal (MoM) articulations can portend catastrophic failure due to adverse local tissue reactions (ALTR). Here, we identified biological and molecular differences between periacetabular synovial tissues of patients with MoM THA failure undergoing revision THA compared to patients undergoing primary THA for routine osteoarthritis (OA). Analysis of tissue biopsies by RNA-sequencing (RNA-seq) revealed that MoM patient samples exhibit significantly increased expression of immune response genes but decreased expression of genes related to extracellular matrix (ECM) remodeling. Thus, interplay between local tissue inflammation and ECM degradation may account for the pathology and compromised clinical outcomes in select patients with MoM implants. We conclude that adverse responses of host tissues to implant materials result in transcriptomic modifications in patients with MoM implants that permit consideration of strategies that could mitigate ECM damage.
•Tissues exposed to CoCr debris exhibit a distinct gene expression profile•CoCr exposure increased expression of genes involved in inflammatory response•Gene expression of ECM proteins is reduced in the presence of CoCr debris•CoCr presence results in elevated expression of genes encoding Ferratin subunits•Gene expression analysis may provide a diagnostic tool to monitor metallic implants