Ultrahigh molecular weight polyethylene particles have direct effects on proliferation, differentiation, and local factor production of MG63 osteoblast-like cells

Small particles of ultrahigh molecular weight polyethylene stimulate format ion of foreign-body granulomas and bone resorption. Bone formation may also be affected by wear debris. To determine if wear debris directly affects o steoblasts, we characterized a commercial preparation of ultrahigh molecula r weight polyethylene (GUR4150) particles and examined their effect on MG63 osteoblast-like cells. In aliquots of the culture medium containing ultrah igh molecular weight polyethylene, 79% of the particles were less than 1 mu m in diameter, indicating that the cells were exposed to particles of less than 1 mu m. MG63 cell response to the particles was measured by assaying cell number, [H-3]thymidine incorporation, alkaline phosphatase specific ac tivity, osteocalcin production, [S-35]sulfate incorporation, and production of prostaglandin E-2 and transforming growth factor-beta. Cell number and [H-3]thymidine incorporation were increased in a dose-dependent manner. Alk aline phosphatase specific activity, a marker of cell differentiation for t he cultures, was significantly decreased, but osteocalcin production was no t affected. [S-35]sulfate incorporation, a measure of extracellular matrix production, was reduced. Prostaglandin E-2 release was increased, but trans forming growth factor-beta production was decreased in a dose-dependent man ner. This shows that ultrahigh molecular weight polyethylene particles affe ct MG63 proliferation, differentiation, extracellular matrix synthesis, and local factor production. These effects were direct and dose dependent. The findings suggest that ultrahigh molecular weight polyethylene wear debris particles with an average size of approximately 1 mu m may inhibit bone for mation by inhibiting cell differentiation and reducing transforming growth factor-beta production and matrix synthesis. In addition, increases in pros taglandin E-2 production may not only affect osteoblasts by an autocrine pa thway but may also stimulate the proliferation and activation of cells in t he monocytic lineage. These changes favor decreased bone formation and incr eased bone resorption as occur in osteolysis.