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Simultaneous labeling of mast cell proteases and protease mRNAs at the bone-implant interface of aseptically loosened
1Department of Orthopaedic Surgery, Orthopaedic Research Laboratory, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0694, USA.
Abstract:
Human mast cells (MC) exhibit two distinct phenotypes based on the protease content of their secretory granules. MC(TC) cells express tryptase, chymase, cathepsin G, and mast cell carboxypeptidase, while MC(T) cells express only tryptase. Both mast cell phenotypes were assessed near regions of osteolysis in uninfected failed joint implants by immunohistochemistry with antibodies to tryptase and chymase, and by in situ hybridization with anti-sense RNA probes for the respective mRNA molecules. Specimens from the interface membrane of 32 aseptically loosened total hip implants were studied, 28 of which had mast cells of the MC(TC) type. Most of these mast cells were aligned along the bone-prosthesis interface adjacent to loosened implants, suggesting involvement in the chronic inflammatory response that leads to bone resorption. Further ultrastructural evidence of mast cells in tissues from failed joint interface membranes was shown by transmission electron microscopy, and detection by staining after magnetic activated cell sorting. The presence of MC at the periprosthetic interface of eroded bone suggests MC degranulation and activity are associated with osteolysis in failed joint prostheses.
Insights
Human mast cells (MC) near failed joint implants are primarily the MC(TC) type. These cells are located near bone erosion, suggesting their involvement in osteolysis and implant loosening.
Area of Science:
- Immunology
- Orthopedic Surgery
- Cell Biology
Background:
- Human mast cells (MCs) exist in two phenotypes: MC(TC) and MC(T).
- MC(TC) cells contain tryptase, chymase, cathepsin G, and carboxypeptidase.
- MC(T) cells contain only tryptase.
Purpose of the Study:
- To investigate the presence and phenotype of mast cells in the interface membrane of aseptically loosened total hip implants.
- To determine the association of mast cells with osteolysis in failed joint prostheses.
Main Methods:
- Immunohistochemistry using antibodies for tryptase and chymase.
- In situ hybridization with anti-sense RNA probes for mRNA.
- Transmission electron microscopy.
- Magnetic activated cell sorting.
Main Results:
- Mast cells, predominantly of the MC(TC) phenotype, were identified in 32 aseptically loosened hip implant specimens.
- MC(TC) cells were frequently observed along the bone-prosthesis interface adjacent to areas of osteolysis.
- Ultrastructural analysis confirmed mast cell presence and suggested degranulation.
Conclusions:
- The MC(TC) mast cell phenotype is present at the periprosthetic interface in failed joint implants.
- Mast cell presence and activity are associated with osteolysis and bone resorption around loosened implants.
- These findings suggest mast cells play a role in the chronic inflammatory response leading to implant failure.
