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Journal of Bone and Joint Surgery - British Volume, Vol 85-B, Issue 8, 1196-1201.
doi: 10.1302/0301-620X.85B8.13311  
Copyright © 2003 by British Editorial Society of Bone and Joint Surgery
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Imbalance of RANKL/RANK/OPG system in interface tissue in loosening of total hip replacement

J. Mandelin, MSc, PhD, Student1; T.-F. Li, PhD, Visiting Student1; M. Liljeström, MSc, PhD, Student1; M. E. Kroon, MD, Senior Scientist2; R. Hanemaaijer, PhD, Senior Scientist2; S. Santavirta, MD, PhD, Professor of Orthopaedics and Traumatology3; and Y. T. Konttinen, MD, PhD, Professor of Medicine4

1 Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki, Finland.
2 Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
3 Department of Orthopaedics and Traumatology, Helsinki University Hospital, Helsinki, Finland.
4 Department of Medicine/Invärtes Medicin, Helsinki University Hospital and ORTON Orthopaedic Hospital of the Invalidfoundation, Helsinki, Finland.

Correspondence should be sent to Professor Y. T. Konttinen at Biomedicum, PO Box 700, Helsinki University Hospital, FIN-000 29 Helsinki, Finland.

In the differentiation of osteoclasts the differentiation factor (RANKL) interacts with the receptor activator of NF-{kappa}B (RANK) in a direct cell-to-cell contact between osteoblast and (pre)osteoclast. This is inhibited by soluble osteoprotegerin (OPG). The mRNA levels of both RANKL (p < 0.01) and RANK (p < 0.05) were high in peri-implant tissue and RANKL+ and RANK+ cells were found in such tissue. Double labelling also disclosed soluble RANKL bound to RANK+ cells. We were unable to stimulate fibroblasts to express RANKL in vitro, but monocyte activation with LPS gave a fivefold increase in RANK mRNA levels. In contrast to RANKL and RANK expression in peri-implant tissue, expression of OPG was restricted to vascular endothelium. Endothelial cell OPG mRNA levels were regulated by TNF-{alpha} and VEGF, but not by hypoxia. It is concluded that activated cells in the interface tissue overproduce both RANKL and RANK and they can interact without interference by OPG.






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Hip, Knee, Trauma, Upper limb, Foot & Ankle, Paediatrics, Oncology, Spine, Arthroplasty, General