UK Team Find MMP/TIMP Markers for Post-TKA Knee Stiffness

Using data from the synovial fluid of 100 patients, researchers from the UK set out to determine and quantify a link between expression of three proteins (matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and a disintegrin, and metalloproteinases with thrombospondin) and stiffness following total knee replacement (TKA).

Their work, “Stiffness post-total knee replacement: A proof of principle study investigating the effect of gene expression analysis of markers of fibrosis,” appears in the August 2019 edition of The Knee.

The team measured the genetic expression of markers for fibrosis from 15 synovial fluid samples acquired from patients who’d been categorized as “best post-operative range of movement (ROM)” and then an additional 15 samples from patients who’d been categorized as displaying the “worst range of motion.”

The UK-based research team summarized their findings by saying, “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 and extension, there was no statistically significant difference between stiff and non-stiff knees in pre-operative or post-operative OKS [Oxford Knee Score]. There was no difference in the individual components of the individual PCS [Pain Catastrophizing Score] score items nor the PCS total scores when stiff and non-stiff knees were compared.”

“Biological factors, namely gene expression of MMPs [matrix metalloproteinases], TIMPs [tissue inhibitors of matrix metalloproteinases] and ADAMTS, [a disintegrin and metalloproteinases with thrombospondin] may contribute towards post-TKR stiffness.”

“This now warrants further investigation to better understand this relationship based on larger, multi-centre, cohorts.”

Co-author Charles Mann, M.B.B.S., with the Department of Trauma and Orthopaedics at Norfolk and Norwich University Hospital in the UK, elaborated on the study results for OTW, “We had noticed some patients stiffer than others for no obvious reason. Patients should be warned pre-operatively that their range of movement is not guaranteed…that stiffness (and pain) is multifactorial and not necessarily controllable.”