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Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4
A Sabokbar1, Y Fujikawa, J Brett
1Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Headington, UK.
Abstract:
To determine the influence of polymethylmethacrylate (PMMA) wear particles on macrophage-osteoclast differentiation, PMMA particles were added to mouse monocytes which were cocultured with UMR 106 osteoblast-like cells in the presence of 1,25 dihydroxy vitamin D3[1,25(OH)2D3] for up to 7 days on glass coverslips and for up to 14 days on human cortical bone slices. An increase in osteoclast differentiation, as evidenced by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and the extent of lacunar bone resorption, was observed in monocyte cultures to which PMMA had been added. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) added to these cocultures caused considerably less expression of TRAP and significant inhibition of lacunar bone resorption. This inhibitory effect was reversed by the addition of specific neutralizing antibodies to LIF and IL-4. These findings show that PMMA-wear particle-associated macrophages exhibit an enhanced capacity for differentiation to osteoclastic bone-resorbing cells.
Insights
Polymethylmethacrylate (PMMA) wear particles promote macrophage differentiation into bone-resorbing osteoclasts. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) can inhibit this process, suggesting therapeutic potential.
Area of Science:
- Biomaterials Science
- Immunology
- Orthopedics
Background:
- Polymethylmethacrylate (PMMA) is widely used in orthopedic implants.
- Wear particles from PMMA can trigger inflammatory responses.
- Macrophage differentiation into osteoclasts contributes to bone resorption.
Purpose of the Study:
- To investigate the effect of PMMA wear particles on macrophage-osteoclast differentiation.
- To explore the role of Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) in this process.
Main Methods:
- Mouse monocytes were co-cultured with osteoblast-like cells (UMR 106) in the presence of 1,25 dihydroxy vitamin D3.
- PMMA particles were added to the cultures.
- Tartrate-resistant acid phosphatase (TRAP) expression and lacunar bone resorption were measured.
- IL-4 and LIF, along with neutralizing antibodies, were used to assess their effects.
Main Results:
- PMMA particles significantly increased osteoclast differentiation, evidenced by higher TRAP expression and bone resorption.
- Addition of IL-4 and LIF markedly reduced TRAP expression and inhibited bone resorption.
- Neutralizing antibodies to IL-4 and LIF reversed the inhibitory effects.
Conclusions:
- PMMA wear particles enhance macrophage differentiation into osteoclasts.
- IL-4 and LIF play a crucial role in inhibiting PMMA-induced osteoclastogenesis.
- Targeting IL-4 and LIF pathways may offer strategies to mitigate bone loss associated with PMMA debris.
