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Increased Expression of a Novel Osteoclast-Stimulating Factor, ADAM8, in Interface Tissue Around Loosened Hip Prostheses
JAMI MANDELIN, TIAN-FANG LI, MIKA V.J. HUKKANEN, MIKKO LILJESTRÖM, ZHAN-KUN CHEN, SEPPO SANTAVIRTA, UULA KITTI, and YRJÖ T. KONTTINEN
ABSTRACT.
Objective. ADAM8 is a protein of a disintegrin and a metalloproteinase family that can induce osteoclast fusion and activity, perhaps via interactions involving integrin receptors and their cysteine-rich/disintegrin domains. Because loosening of hip replacement implants is characterized by foreign body giant cells and peri-implant osteoclasts, it was speculated that this molecule might be (over)expressed in the synovial membrane-like interface tissues. Methods. In situ hybridization; immunohistochemical staining with or without tartrate-resistant acid phosphatase (TRAP) staining; image analysis/morphometry; isolation, amplification, and cloning of ADAM8; nucleotide sequencing; quantitative reverse transcriptase-polymerase chain reaction (RT-PCR); and Western blot. Results. In situ hybridization disclosed ADAM8 mRNA in mono- and multinuclear cells in both interface and control synovial samples. Quantitative RT-PCR revealed high ADAM8 mRNA copy numbers in interface tissue (p < 0.01). Accordingly, extensive ADAM8 immunoreactivity was observed in the lining-like layers and sublining areas of interface tissue (p < 0.001). A 65 kDa ADAM8 band in Western blot of tissue extracts confirmed these findings. ADAM8/TRAP double staining showed close spatial relationships of ADAM8 positive precursor cells with other precursors and/or TRAP-positive multinuclear cells. Conclusion. ADAM8 is (over)expressed in tissues around aseptically loosened total hip implants, which are characterized by chronic foreign body inflammation and peri-implant bone loss. This is compatible with a role for ADAM8 in the formation of foreign body giant cells and osteoclasts. (J Rheumatol 2003;30:2033-8) Key Indexing Terms:
ADAM8
From the Department of Anatomy, University of Helsinki; Department of Oral Medicine, Institute of Dentistry, University of Helsinki; Department of Medicine/Invärtes Medicin, Helsinki University Hospital; ORTON Research Institute and the Orthopaedic Hospital of the Invalid Foundation, Helsinki; and Department of Orthopaedics and Traumatology, Helsinki University Hospital, Helsinki, Finland. Supported by EVO grant TYH 0341, TYH 8307, TYH 1202, and TYH 0215, the Finnish Academy and Group of Excellence grants (SA, TEKES, Ministry of Education and University of Helsinki), Finska Läkaresällskapet, the Invalid Foundation, and the Sigrid Juselius Foundation. J. Mandelin is supported by a grant from the Emil Aaltonen Foundation. J. Mandelin, MSc, Department of Anatomy, University of Helsinki; T.F. Li, MD, PhD, Department of Anatomy, University of Helsinki, ORTON Research Institute and Orthopaedic Hospital of the Invalid Foundation, Department of Orthopaedics and Traumatology, Helsinki University Central Hospital; M.V.J. Hukkanen, PhD; M. Liljeström, MSc; Z.K. Chen, MD, Department of Anatomy, University of Helsinki; S. Santavirta, MD, PhD, Professor, Department of Orthopaedics and Traumatology, Helsinki University Central Hospital; U. Kitti, DDS, Department of Oral Medicine, Institute of Dentistry, University of Helsinki; Y.T. Konttinen, MD, Professor, Department of Medicine/Invärtes Medicin, Helsinki University Central Hospital, ORTON, and Orthopaedic Hospital of the Invalid Foundation. Address reprint requests to Prof. Y.T. Konttinen, Biomedicum Helsinki, PO Box 700 (Haartamaninkatu 8), FIN-00029 HUS, Finland. E-mail: yrjo.konttinen@helsinki.fi Submitted April 8, 2002; revision accepted February 3, 2003. |