Polymethylmethacrylate particles enhance DNA and protein synthesis of human fibroblasts in vitro

Abstract

Aseptic loosening of polymethylmethacrylate (PMMA) fixed prosthesis is characterized by formation of a radiolucent fibrous membrane, accumulation of inflammatory cells and osteolysis. Since this membrane is produced by fibroblasts, it is likely that these connective tissue cells play a critical role in the loosening process. Whether fibroblasts form the radiolucent membrane in response to stimulation by PMMA has not yet been established, nor is it known whether fibroblasts play a role in attracting inflammatory cells to the bone-cement interface by secreting chemical mediators. To address this question, we analyzed the in vitro response of normal human fibroblasts to PMMA. Cells were plated with 10(5)/mL Dulbecco minimal essential medium and were incubated 4 h later with PMMA particles, polystyrene (PS) particles, or medium alone. Proliferative capacity monitored by incorporation of 3H-thymidine was significantly increased following a 48 h exposure to PMMA. Protein synthesis determined by incorporation of 14C-leucine and 14C-proline was also increased. In contrast, levels of secreted prostaglandin (PG) E2 assayed immunoenzymatically was not altered by PMMA. Fibroblasts exposed to control PS did not change their proliferative or protein synthetic activity. Fibroblasts internalized PMMA and PS particles without detectable ultrastructural damage. PMMA enhancement of fibroblast proliferative capacity and protein synthetic ability observed in our in vitro assay system suggests similar effects on fibroblasts in vivo.

Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture

“…Two previous studies have shown a humeral interaction between macrophages and fibroblasts. 9,15 Conditioned medium from macrophages exposed to phagocytosable particles induced a proliferative response in fibroblasts. Macrophage-fibroblast interactions involving cytokine release have been described previously.…”

Effect of prosthetic titanium wear debris on mitogen-induced monocyte and lymphoid activation

“…Commercially prepared polybead PMMA and PS microspheres measuring .325 micrometers in diameter were obtained from Polysciences (Warrington, Pennsylvania) and were sterilized by exposure to UV irradiation overnight, as previously described. 20 These particles were screened for endotoxin using a Sigma Biosciences endotoxin kit assay. There was no detectable endotoxin in the particles used in this study.…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20] These studies, which have documented the direct effect of particle wear debris, such as titanium alloy, polyethylene, and polymethylmethacrylate particles, on monocyte/macrophage function, used either commercially prepared particles or particulate wear debris retrieved from revision surgery. Exposure of monocytes/macrophages and synoviocytes to these particles resulted in the release of inflammatory cytokines, [10][11][12][13][14][15][16][17][18][19][20][21][22] demonstrating that wear particles may directly activate mononuclear inflammatory cells.…”

G-protein activity requirement for polymethylmethacrylate and titanium particle-induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 releasein vitro

“…65 Frondoza et al, Maloney et al, and Manlapaz et al reported that fibroblasts respond to PMMA particles and metallic particles through increased cell proliferation and release of proinflammatory cytokines and degradative enzymes. 29,66,67 Fibroblasts also respond to particulate debris through the release of prostaglandin E2, IL-6, and up-regulation of collagenase activity. 29,33 Different distributions of cell types in membranes harvested from different patients undergoing revision arthroplasty suggest that the response to orthopedic wear debris may be patient specific.…”