Differential proteomic analysis of synovial fluid from hip arthroplasty patients with a pseudotumor vs. Periprosthetic osteolysis

J Orthop Res. 2018 Jul;36(7):1849-1859. doi: 10.1002/jor.23858. Epub 2018 Mar 14.


Adverse tissue reactions to metal implants, including pseudotumors, can compromise implant functionality and survivorship. The identification of specific proteins in the synovial fluid (SF) of hip arthroplasty patients with a pseudotumor may lead to a better understanding of the underlying pathomechanisms. The objective of the present study was to compare the protein content of SF from patients with a short-term metal-on-metal hip implant associated with a pseudotumor and patients with a long-term metal-on-polyethylene hip implant associated with periprosthetic osteolysis. Discovery proteomics was used to identify differentially abundant proteins in albumin-depleted SF. In toto, 452 distinct proteins (present in at least half of the patients in one or both groups) were identified. Thirty of these 452 proteins were differentially abundant between the two groups, including two potential biomarkers: 6-phosphogluconate dehydrogenase (which plays a major protective role against oxidative stress) for the pseudotumor group, and scavenger receptor cysteine-rich type 1 protein M130 (which is involved in low-grade inflammation) for the periprosthetic osteolysis group. Other differentially abundant proteins identified suggest the presence of an adaptive immune response (particularly a type-IV hypersensitivity reaction), necrosis, and greater oxidative stress in patients with a pseudotumor. They also suggest the presence of an innate immune response, oxidative stress, tissue remodeling, and apoptosis in both patient groups, although differences in the specific proteins identified in each group point to differences in the pathomechanisms. Overall, results provide insights into the molecular mechanisms underlying metal-related pseudotumors and periprosthetic osteolysis, and may ultimately help elucidate pseudotumor etiology and assess the risk that asymptomatic pseudotumors will develop into an aggressive lesion. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1849-1859, 2018.

Keywords: hip implant; pathomechanisms; proteomics; pseudotumor; synovial fluid.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Arthroplasty, Replacement, Hip
  • Biomarkers / metabolism
  • Female
  • Hip Joint / pathology
  • Hip Prosthesis / adverse effects*
  • Humans
  • Immunity, Innate
  • Inflammation
  • Male
  • Mass Spectrometry
  • Metal-on-Metal Joint Prostheses / adverse effects*
  • Middle Aged
  • Necrosis
  • Osteolysis / etiology*
  • Oxidative Stress
  • Phosphogluconate Dehydrogenase / metabolism
  • Polyethylene / chemistry*
  • Prosthesis Design
  • Prosthesis Failure*
  • Proteins / metabolism
  • Proteome
  • Retrospective Studies
  • Synovial Fluid / metabolism*


  • Biomarkers
  • Proteins
  • Proteome
  • Polyethylene
  • Phosphogluconate Dehydrogenase