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Published on: April 6, 2022
Expression of caspase-1 in synovial membrane-like interface tissue around loosened hip prostheses
T F Li1, J Mandelin, M V J Hukkanen
1ORTON Research Institute, the Orthopaedic Hospital of the Invalid Foundation, Helsinki, Finland.
Abstract:
Caspase-1 expression in synovial membrane-like interface tissue (SMLIT) around loosened hip prostheses and osteoarthritic synovial samples was studied. Caspase-1 mRNA was found in SMLIT and synovial tissue. There is no difference in the copy numbers of caspase-1 mRNA between these samples. Both precursor and active forms of caspase-1 proteins appeared in these samples, but the number of positive cells was higher in SMLIT than in synovial tissue. Double labeling revealed that most caspase-1-positive cells were macrophages and fibroblasts. In the lining-like layers and deep stroma of SMLIT, many cells were double positive for active caspase-1 and interleukin-1 beta (IL-1beta). In contrast, the number of active caspase-1/IL-18 double-positive cells was very low. We conclude that caspase-1 synthesis is increased in SMLIT. Caspase-1 can be involved in implant loosening by processing IL-1beta precursor into its mature form, which is a potent osteoclast-activating factor and a major proinflammatory mediator.
Insights
Increased caspase-1 (an enzyme) synthesis in tissue around loose hip implants may drive inflammation and bone loss by activating interleukin-1 beta (IL-1beta). This suggests a role for caspase-1 in implant loosening.
Area of Science:
- Biomedical Engineering
- Immunology
- Orthopedics
Background:
- Implant loosening is a major complication of hip arthroplasty.
- The role of inflammatory mediators in implant loosening is not fully understood.
Purpose of the Study:
- To investigate the expression and localization of caspase-1 in synovial membrane-like interface tissue (SMLIT) from loosened hip prostheses.
- To compare caspase-1 expression in SMLIT with osteoarthritic synovial tissue.
Main Methods:
- Quantitative analysis of caspase-1 mRNA.
- Immunohistochemical detection of precursor and active caspase-1 proteins.
- Double-labeling for caspase-1 with cell markers (macrophages, fibroblasts) and cytokines (IL-1beta, IL-18).
Main Results:
- Caspase-1 mRNA and protein were detected in both SMLIT and synovial tissue.
- Higher numbers of caspase-1-positive cells, primarily macrophages and fibroblasts, were found in SMLIT.
- Increased co-localization of active caspase-1 with IL-1beta was observed in SMLIT.
Conclusions:
- Caspase-1 synthesis is upregulated in SMLIT associated with loosened hip prostheses.
- Caspase-1 may contribute to implant loosening by processing IL-1beta, a key factor in osteoclast activation and inflammation.
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