Abstract
ObjectiveAseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15–20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists.DesignThe inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry.ResultsAL tissues had elevated levels of TNF-family members sTNFR2, TNFSF14, sFasL, sBAFF, cytokines/chemokines IL8, CCL2, IL1RA/IL36, sIL6R, and growth factors sAREG, CSF1, comparing to non-AL. High interindividual variability in protein levels was evident particularly in non-AL. Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between AL and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts. The source of elevated inflammatory molecules was macrophages and multinucleated osteoclast-like cells in AL and histiocytes and osteoclast-like cells in non-AL tissues, respectively. All proteins were present in higher levels in osteoclast-like cells than in macrophages.ConclusionsOur study revealed a differential inflammation signature between AL and non-AL stages of TKA. It also highlighted the unique patient’s response to TKA in non-AL stages. Further confirmation of our preliminary results on a larger cohort is needed. Analysis of the time-axis of processes ongoing around TKA implantation may help to understand the mechanisms driving periprosthetic bone resorption needed for diagnostic/preventative strategies.
Highlights
Total knee arthroplasty (TKA) is one of the most effective therapies of end-stage osteoarthritis with growing numbers of patients operated each year worldwide [1]
Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between Aseptic loosening (AL) and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts
All proteins were present in higher levels in osteoclast-like cells than in macrophages
Summary
Total knee arthroplasty (TKA) is one of the most effective therapies of end-stage osteoarthritis with growing numbers of patients operated each year worldwide [1]. Aseptic loosening (AL) is the most common late failure of TKA with estimated occurrence about 15–20% of patients in a 20-year time horizon [2]. It is always accompanied with periprosthetic osteolysis (PPOL), which is a scientific synonym for clinically observed bone defects. These complicate the reoperation of aseptically loosened TKA, increase its cost, and limit survivorship of the revision TKA. Some researchers emphasize the role of tissue inflammation stimulated in the response to prosthetic byproducts by innate immunity network like in total hip arthroplasty (THA) [3, 4]
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