Small particles of ultrahigh molecular weight
polyethylene stimulate formation of
foreign-body granulomas and
bone resorption. Bone formation may also be affected by wear debris. To determine if wear debris directly affects osteoblasts, we characterized a commercial preparation of ultrahigh molecular weight
polyethylene (GUR4150) particles and examined their effect on MG63 osteoblast-like cells. In aliquots of the culture medium containing ultrahigh molecular weight
polyethylene, 79% of the particles were less than 1 microm in diameter, indicating that the cells were exposed to particles of less than 1 microm. MG63 cell response to the particles was measured by assaying cell number, [3H]
thymidine incorporation,
alkaline phosphatase specific activity,
osteocalcin production, [35S]
sulfate incorporation, and production of
prostaglandin E2 and
transforming growth factor-beta. Cell number and [3H]
thymidine incorporation were increased in a dose-dependent manner.
Alkaline phosphatase specific activity, a marker of cell differentiation for the cultures, was significantly decreased, but
osteocalcin production was not affected. [35S]
sulfate incorporation, a measure of extracellular matrix production, was reduced.
Prostaglandin E2 release was increased, but
transforming growth factor-beta production was decreased in a dose-dependent manner. This shows that ultrahigh molecular weight
polyethylene particles affect 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 microm may inhibit bone formation by inhibiting cell differentiation and reducing
transforming growth factor-beta production and matrix synthesis. In addition, increases in
prostaglandin E2 production may not only affect osteoblasts by an autocrine pathway but may also stimulate the proliferation and activation of cells in the monocytic lineage. These changes favor decreased bone formation and increased
bone resorption as occur in
osteolysis.