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Induction of matrix metalloproteinase expression in human macrophages by orthopaedic particulate debris in vitro
Y Nakashima1, D H Sun, W J Maloney
1Division of Orthopaedic Surgery, Stanford University School of Medicine, California 94305-5326, USA.
Abstract:
We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 microm in size. Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle. Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues.
Insights
Human macrophages exposed to metal and bone-cement particles release matrix metalloproteinases (MMPs). This study shows particle debris stimulates MMP-1, MMP-2, and MMP-9 release, crucial for understanding periprosthetic tissue reactions.
Area of Science:
- Biomedical Engineering
- Immunology
- Materials Science
Background:
- Periprosthetic osteolysis is a major cause of implant failure.
- Particulate debris from metal alloys and bone cement are implicated in this process.
- Macrophages are key immune cells involved in the foreign body response.
Purpose of the Study:
- To investigate the effect of metal and bone-cement particles on macrophage matrix metalloproteinase (MMP) release.
- To determine the specific MMPs involved and their expression levels.
- To support the hypothesis linking particulate debris to MMP production in periprosthetic tissues.
Main Methods:
- Human macrophages were isolated from peripheral blood.
- Macrophages were exposed to titanium alloy and polymethylmethacrylate (PMMA) particles (0.2-10 µm).
- Zymography, Western immunoblotting, and Northern blotting were used to analyze gelatinase and collagenolytic activity and MMP mRNA levels.
Main Results:
- Titanium alloy and PMMA particles induced dose- and time-dependent release of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2).
- Increased release of MMP-1 and elevated mRNA levels for MMP-1, MMP-2, and MMP-9 were observed.
- Collagenolytic activity in the macrophage culture medium also increased in response to particle exposure.
Conclusions:
- Macrophages release specific matrix metalloproteinases (MMPs) in response to metal and bone-cement particles.
- The findings support the hypothesis that the amount of particulate debris correlates with MMP release in periprosthetic tissues.
- This highlights the role of macrophages and MMPs in the pathogenesis of periprosthetic osteolysis.
