Dean D D, Schwartz Z, Blanchard C R, Liu Y, Agrawal C M, Lohmann C H, Sylvia V L, Boyan B D
Department of Orthopaedics, University of Texas Health Science Center, San Antonio 78284-7774, USA.
J Orthop Res. 1999 Jan;17(1):9-17. doi: 10.1002/jor.1100170104.
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.
超高分子量聚乙烯的小颗粒会刺激异物肉芽肿的形成和骨吸收。骨形成也可能受到磨损碎屑的影响。为了确定磨损碎屑是否直接影响成骨细胞，我们对一种超高分子量聚乙烯（GUR4150）颗粒的商业制剂进行了表征，并研究了它们对MG63成骨样细胞的影响。在含有超高分子量聚乙烯的培养基等分试样中，79%的颗粒直径小于1微米，这表明细胞暴露于直径小于1微米的颗粒中。通过检测细胞数量、[3H]胸腺嘧啶核苷掺入、碱性磷酸酶比活性、骨钙素产生、[35S]硫酸盐掺入以及前列腺素E2和转化生长因子-β的产生来测量MG63细胞对颗粒的反应。细胞数量和[3H]胸腺嘧啶核苷掺入呈剂量依赖性增加。碱性磷酸酶比活性作为培养物细胞分化的标志物显著降低，但骨钙素产生未受影响。[35S]硫酸盐掺入作为细胞外基质产生的指标降低。前列腺素E2释放增加，但转化生长因子-β产生呈剂量依赖性降低。这表明超高分子量聚乙烯颗粒会影响MG63的增殖、分化、细胞外基质合成和局部因子产生。这些影响是直接的且呈剂量依赖性。研究结果表明，平均尺寸约为1微米的超高分子量聚乙烯磨损碎屑颗粒可能通过抑制细胞分化、减少转化生长因子-β产生和基质合成来抑制骨形成。此外，前列腺素E2产生的增加不仅可能通过自分泌途径影响成骨细胞，还可能刺激单核细胞系细胞的增殖和活化。这些变化有利于骨形成减少和骨吸收增加，如同在骨质溶解中发生的那样。
