Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/51908
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Type: Journal article
Title: The induction of a catabolic phenotype in human primary osteoblasts and osteocytes by polyethylene particles
Author: Atkins, G.
Welldon, K.
Holding, C.
Haynes, D.
Howie, D.
Findlay, D.
Citation: Biomaterials, 2009; 30(22):3672-3681
Publisher: Elsevier Sci Ltd
Issue Date: 2009
ISSN: 0142-9612
1878-5905
Statement of
Responsibility: 
Gerald J. Atkins, Katie J. Welldon, Christopher A. Holding, David R. Haynes, Donald W. Howie and David M. Findlay
Abstract: Polyethylene (PE) wear particles are associated with the osteolysis seen in aseptic loosening that leads to orthopaedic implant failure. While cells of the monocyte/macrophage lineage are implicated, evidence is now emerging that osteoblastic cells may also be affected by PE. In this study we investigated the effect of PE particles on osteoblasts, using a novel in vitro cell culture system that was developed to juxtapose cells and PE particles, replicating the 3-dimensional (3D) environment near implants. This system allowed normal human bone-derived cells (NHBC) to undergo differentiation into a mature osteocyte-like phenotype over a 21–28-day culture period. PE particles induced an increase in mRNA expression of the osteocyte markers E11, DMP-1 and SOST/sclerostin. NHBC responded to PE particles by increasing the mRNA expression of several genes associated with osteoclast formation and activity (RANKL, IL-8 and M-CSF) and decreased the expression of the osteoclast antagonist, OPG. PE also appeared to induce a switch in the RUNX2 control of gene expression from that of promoting matrix production (type I collagen) to inducing the expression of pro-osteoclastogenic genes. These results suggest that PE particles switch mature osteoblastic cells from an anabolic to a more catabolic phenotype. This concept was further supported by the finding that PE-induced expression of RANKL mRNA in the mouse osteocyte cell line, MLO-Y4. Overall, our results suggest that PE particles directly induce a change in the phenotype of mature osteoblasts and osteocytes, consistent with the net loss of bone near orthopaedic implants.
Keywords: Polyethylene; Osteolysis; Human osteoblasts; Osteocytes; MLO-Y4; Wear particles
RMID: 0020090990
DOI: 10.1016/j.biomaterials.2009.03.035
Appears in Collections:Orthopaedics and Trauma publications

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