Stiffness post-total knee replacement: A proof of principle study investigating the effect of gene expression analysis of markers of fibrosis

Knee. 2019 Aug;26(4):914-922. doi: 10.1016/j.knee.2019.05.005. Epub 2019 Jun 5.

Abstract

Background: To establish proof of principle of a link between phenotypic expression and stiffness after TKR.

Methods: From 100 patients, genetic expression of markers of fibrosis was performed for 15 synovial samples from patients categorised as 'best post-operative range of movement (ROM)' and 15 samples from patients with 'worst ROM'. These markers included Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteinases with Thrombospondin (ADAMTS) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs). Genetic marker data were compared to Oxford Knee Scores (OKS) and Pain Catastrophizing Scores (PCS).

Results: Quantitative markers for gene expression demonstrated more outliers in stiff compared to non-stiff knees, suggesting a greater imbalance in pro- and anti-fibrotic markers in stiff knees. Whilst there was a significant difference in the range of post-operative knee flexion (p = 0.001) and extension (p = 0.001), there was no statistically significant difference between stiff and non-stiff knees in pre-operative or post-operative OKS (p ≥ 0.06). There was no difference in the individual components of the individual PCS score items nor the PCS total scores when stiff and non-stiff knees were compared (p > 0.05).

Conclusion: Biological factors, namely gene expression of MMPs, TIMPs and ADAMTS, may contribute towards post-TKR stiffness. This now warrants further investigation to better understand this relationship based on larger, multi-centre, cohorts.

Level of evidence: Level 3.

Keywords: Arthrofibrosis; Case–control; Gene expression; Knee arthroplasty; Limited range.

MeSH terms

  • ADAMTS Proteins / genetics
  • ADAMTS Proteins / metabolism
  • Aged
  • Arthroplasty, Replacement, Knee / adverse effects*
  • Biomarkers / metabolism
  • Female
  • Fibrosis / metabolism
  • Fibrosis / physiopathology
  • Humans
  • Knee Joint / pathology*
  • Knee Joint / physiopathology*
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Middle Aged
  • Postoperative Complications
  • RNA / metabolism
  • Range of Motion, Articular / physiology*
  • Synovial Fluid / metabolism
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • Biomarkers
  • Tissue Inhibitor of Metalloproteinases
  • RNA
  • ADAMTS Proteins
  • Matrix Metalloproteinases