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521 POLYMETHYLMETHACRYLATE PARTICLES INHIBIT OSTEOBLASTIC DIFFERENTIATION OF BONE MARROW OSTEOPROGENITOR CELLS IN VITRO.
  1. R. Chiu*,
  2. T. Ma*,
  3. R. L. Smith*,
  4. S. B. Goodman*
  1. *Stanford University School of Medicine, Stanford, CA

Abstract

Purpose Particulate debris generated from orthopedic implants induces osteolysis at the bone-implant interface, causing the prosthesis to become unstable. Bone regeneration in the prosthetic bed depends on the activity of osteoblasts and their differentiation from osteoprogenitors in the bone marrow. This study investigated the effects of wear particles of polymethylmethacrylate (PMMA), a prosthetic material, on the ability of bone marrow osteoprogenitor cells to differentiate into functional osteoblasts in vitro.

Methods Bone marrow cells isolated from the femurs and tibias of C57 mice were grown in osteogenic medium containing 10-7 M dexamethasone, 50 μg/mL ascorbic acid, and 10 mM β-glycerophosphate. Cell cultures were challenged with PMMA particles at concentrations of 0.038%, 0.075%, 0.150%, 0.300%, and 0.600% v/v on the initial day (day 0) of growth in osteogenic medium. Three additional cultures were challenged with particles on the 5th, 10th, and 15th day of growth in osteogenic medium to assess the particle effects at later stages of differentiation. All cultures were grown for 15 days past the time of particle addition, after which the cells were measured for the levels of bone mineralization, alkaline phosphatase expression, and cell proliferation. In a time course experiment, measurements were taken at 5-day intervals for the cultures challenged with 0.300% v/v PMMA on the initial day of growth in osteogenic medium.

Results Addition of PMMA particles to bone marrow cells on the first day (day 0) of growth in osteogenic medium resulted in a dose-dependent decrease in bone mineralization, alkaline phosphatase expression, and cell proliferation, with complete suppression of osteoblastic phenotype observed at particle concentrations ≥ 0.300% v/v. Cells challenged with 0.300% v/v PMMA on the first day of differentiation showed no rise in bone mineralization, alkaline phosphatase expression, and cell proliferation throughout the entire culture period. Cells treated with particles on the 5th, 10th, and 15th day of growth in osteogenic medium showed insignificant reductions in bone mineralization and alkaline phosphatase expression.

Conclusions This study has demonstrated that PMMA particles suppress osteoprogenitor differentiation and function. The strongest inhibitory effects are observed when the cells are challenged within the first 5 days of osteoblastic differentiation. Beyond this time frame, the osteoprogenitors become less sensitive to particle treatment as they develop from relatively undifferentiated progenitors into mature osteoblasts.

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