The effect of ultra-high molecular weight polyethylene wear debris on MG63osteosarcoma cells in vitro

Background Focal osteolysis due to ultra-high molecular weight polyethylene wear debris involves effects on both bone resorption and bone formation. Methods: The response of MG63 osteoblast-like osteosarcoma cells to ultra-h igh molecular weight polyethylene wear debris isolated by enzymatic digesti on of granulomatous tissue obtained from the sites of failed total hip arth roplasties was examined, Scanning electron microscopy, particle-size analys is, and Fourier transform infrared spectroscopy were used to characterize t he number, morphology, size distribution, and chemical composition of the p articles. Cell response was assessed by adding particles at varying dilutio ns to confluent cultures and measuring changes in cell proliferation (numbe r of cells and [H-3]-thymidine incorporation), osteoblast function (alkalin e-phosphatase-specific activity and osteocalcin production), matrix product ion (collagen production and proteoglycan sulfation), and local cytokine pr oduction (prostaglandin-E-2 production), Results: The mean size of the particles was 0.60 micrometer, and 95 percent of the particles had a size of less than 1.5 micrometers. The number of pa rticles per gram of tissue ranged from 1.39 to 3.38 x 10(9). Three of the f our batches of particles were endotoxin-free. Exposure of the cells to part icles of wear debris significantly increased the number of cells (p < 0.05) and the [H-3]-thymidine incorporation (p < 0.05) in a dose-dependent manne r, Im contrast, the addition of particles de creased alkaline-phosphatase-s pecific activity and osteocalcin production. Collagen production and proteo glycan sulfation were also decreased, while prostaglandin-E-2, synthesis wa s increased by the addition of particles; Conclusions: Ultra-high molecular weight polyethylene particles isolated fr om human tissue stimulated osteoblast proliferation and prostaglandin-E-2 p roduction and inhibited cell differentiation and matrix production. These r esults indicate that particles of wear debris inhibit cell functions associ ated,vith hone formation and that osteoblasts may produce factors in respon se to wear debris that influence neighboring cells, such as osteoclasts and macrophages. Clinical Relevance: Particles of wear debris, especially ultra-high molecul ar weight polyethylene, have been implicated in the loosening of implants a nd the development of osteolysis. The present study shows that particles of ultra-high molecular weight polyethylene isolated from human tissue inhibi t osteoblast functions associated,vith bone formation. In addition, particl es of wear debris induced osteoblasts to secrete factors capable of influen cing neighboring cells, such as osteoclasts and macrophages. These results suggest that osteoblasts may play a role in the cascade of events leading t o granuloma formation, osteolysis, and failure of orthopaedic implants.