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Fibroblast apoptosis and caspase-8 activation in aseptic loosening
1Human Anatomy Laboratory, Research Center for Biocompatibility, Medical Sciences Department, University of Eastern Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
Abstract:
The presence of apoptosis has been investigated in the interface membranes collected during revision surgery of loosened total hip joint arthroplasty (THAs). Terminal deoxyrobonucleotidyl transferase (TdT) assay for apoptotic DNA fragmentation quantification revealed a statistically significant presence of apoptosis in aseptic samples, obtained from both cementless (2.37+/-0.6%) and cemented (12.01+/-1%) prosthesis compared to septic samples where apoptosis was almost absent. Activated caspase-8 immunostaining was almost undetectable in septic samples, while in the aseptic samples active caspase-8 was present weakly in the cementless samples (1.35+/-0.22%) and strongly in the cemented ones (9.0+/-0.40%). The caspase-8 cytoplasmatic staining allowed the morphological recognition of positive cells both as fibroblast-like and immunocompetent cells. In aseptic cemented samples fibroblast-like cells were the most represented subpopulation in the caspase-8 positive population scored (76.6%) compared to the immunocompetent cells (23.4%). Caspase-8 activation is an upstream event in the apoptotic pathway triggered by the activation of cytokines receptors such as TNF-alpha receptor 1 (TNFR-1), and the presence of caspase-8 activation in fibroblast-like cells in the aseptic interface membranes of THAs suggests a possible TNF-alpha dependent apoptosis.
Insights
Apoptosis is present in aseptic loosened hip implants, particularly in cemented ones. This suggests a potential TNF-alpha-dependent cell death pathway in fibroblast-like cells within these interface membranes.
Area of Science:
- Orthopedic Surgery
- Cell Biology
- Biomaterials Science
Background:
- Loosened total hip arthroplasty (THA) is a significant clinical challenge.
- Interface membranes form around loosened THAs, influencing implant survival.
- Understanding cellular mechanisms like apoptosis in these membranes is crucial.
Purpose of the Study:
- To investigate the presence and characteristics of apoptosis in interface membranes from loosened THAs.
- To compare apoptosis levels in aseptic versus septic loosening.
- To identify cell types involved in apoptosis and potential pathways.
Main Methods:
- Analysis of interface membranes from revision THA surgery.
- Terminal deoxyrobonucleotidyl transferase (TdT) assay for DNA fragmentation.
- Caspase-8 immunostaining to assess apoptosis activation.
- Morphological identification of positive cells (fibroblast-like and immunocompetent).
Main Results:
- Significant apoptosis detected in aseptic samples (cementless and cemented), but not in septic samples.
- Activated caspase-8 was significantly higher in aseptic cemented samples (9.0%) compared to cementless (1.35%).
- Fibroblast-like cells were the predominant caspase-8 positive population in aseptic cemented membranes (76.6%).
Conclusions:
- Apoptosis is a key feature of aseptic loosening in THA interface membranes.
- Caspase-8 activation, particularly in fibroblast-like cells, suggests a potential TNF-alpha-dependent apoptotic pathway.
- Findings highlight differences between aseptic and septic loosening mechanisms.