Ectopic expression of macrophage scavenger receptor MARCO in synovial membrane-like interface tissue in aseptic loosening of total hip replacement implants
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Published on: October 20, 2013
De-Sheng Zhao1, Guo-Feng Ma, Mikko Selenius
1Institute of Biomedicine/Medicine, University of Helsinki, P.O. Box 63, Haartmaninkatu 8, Biomedicum Helsinki, 00014 Helsinki, Finland.
Abstract:
Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor with a very limited expression in healthy tissues. It was hypothesized that foreign body wear debris induces it to participate in handling of implant-derived particles in human synovial membrane-like tissue around aseptically loosening total hip replacement implants. A DNA microarray study showed that MARCO was upregulated in human monocytes by polymethyl methacrylate particles in cell culture. MARCO mRNA and protein were strongly expressed in numerous CD68 positive macrophages and foreign body giant cells in interface membrane lining and stroma around cemented implants, but was only present in a few cells in synovial membrane from osteoarthritis patients. A 65-kDa MARCO-reactive band was only found in interface tissue extracts. This is the first work to show upregulation of MARCO mRNA by foreign bodies in vitro. This is paralleled in vivo as MARCO mRNA and protein were over-expressed in chronic foreign body synovitis. As scavenger receptor MARCO apparently participates in handling of wear particles, which due to their nondegradable, irritating nature initiate/perpetuate foreign body inflammation, and peri-implant osteolysis.
Insights
Foreign body debris upregulates the scavenger receptor MARCO (macrophage receptor with collagenous structure) in cells around hip implants. This suggests MARCO plays a role in implant wear particle inflammation and bone loss.
Area of Science:
- Biomedical Engineering
- Immunology
- Orthopedic Research
Background:
- Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor with limited expression in healthy tissues.
- Aseptic loosening of total hip replacement implants involves foreign body reactions to wear debris.
- The role of MARCO in handling implant-derived particles in the human synovial membrane is not well understood.
Purpose of the Study:
- To investigate the expression and role of MARCO in the human synovial membrane around aseptically loosening total hip replacement implants.
- To determine if foreign body wear debris induces MARCO expression in vitro and in vivo.
Main Methods:
- DNA microarray analysis of human monocytes treated with polymethyl methacrylate particles.
- Immunohistochemical analysis of MARCO mRNA and protein expression in interface membrane tissue from hip replacement patients and osteoarthritis patients.
- Western blot analysis of interface tissue extracts.
Main Results:
- Polymethyl methacrylate particles upregulated MARCO mRNA in human monocytes in cell culture.
- MARCO mRNA and protein were highly expressed in macrophages and foreign body giant cells in the interface membrane around cemented implants.
- MARCO expression was significantly lower in synovial membranes from osteoarthritis patients.
- A 65-kDa MARCO-reactive band was detected in interface tissue extracts.
Conclusions:
- This study demonstrates, for the first time, the upregulation of MARCO mRNA by foreign bodies in vitro.
- MARCO is overexpressed in vivo in chronic foreign body synovitis around hip implants.
- The scavenger receptor MARCO appears to be involved in the handling of wear particles, contributing to foreign body inflammation and peri-implant osteolysis.
