 |
|
|
 |
EARL R. BOGOCH, TODD C. LEE, VICTOR L. FORNASIER, and STUART A. BERGER
ABSTRACT. Methods. Peripheral blood, femoral bone marrow, and spleen cells were harvested from carrageenan-induced arthritis Sprague-Dawley rats; fluorescence stained for CD3, CD8, CD4, CD11b/c, anti-mononuclear phagocyte (MNP), CD3/CD8, CD3/CD4, and MNP/CD11b/c; and evaluated by flow cytometry. Arthritis was induced in New Zealand white rabbits in 5 treatment groups: normal, arthritis, zoledronate-treated from arthritis induction, or 2 or 4 weeks after induction. Animals were euthanized after 7 weeks and distal femoral condyles were decalcified, processed, sectioned, and stained. Sections were evaluated for several cell types and histological features relevant to inflammation, which were assigned a categorical grade from 0 (healthy morphology) to 3 (extensive inflammation). Tidemark was evaluated on a continuous scale. Results. Significantly elevated levels of CD3+CD4+ lymphocytes and CD11b/c+MNP+ monocytes were observed in the bone marrow of arthritic rats, consistent with intraosseous inflammation. No corresponding increase was observed in peripheral blood or spleen. In rabbits, the histology of lymphocytes, mononuclear cells, fibrocytes, fibrosis, lipocytes, and plasma cells varied significantly across treatment groups. Controls exhibited normal histology. In arthritis, these cell types and tissues displayed a shift of 1–2 grades higher (toward inflammation). Intact tidemark was reduced. Following zoledronate treatment, mononuclear cells, fibrocytes, fibrosis, and lipocytes were significantly altered toward normal, and tidemark shifted toward normal. Conclusion. Intraosseous bone marrow inflammation was observed in carrageenan-induced inflammatory arthritis in rats and rabbits. Zoledronate administration diminished the intraosseous inflammatory response. (First Release May 15 2007; J Rheumatol 2007;34:1229-40) Key Indexing Terms:
ARTHRITIS
From the Department of Surgery, Division of Orthopaedic Surgery, Li Ka Shing Knowledge Institute and the Martin Family Centre for Arthritis Care and Research, Mobility Program, St. Michael's Hospital, University of Toronto; Faculty of Medicine, University of Toronto; Department of Pathology, St. Michael's Hospital; and the Arthritis and Immune Disorder Research Centre, University Health Network, Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Supported by The Canadian Arthritis Network and The Arthritis Society. E.R. Bogoch, MD, Professor, Department of Surgery, University of Toronto, Director, Mobility Program, St. Michael's Hospital; T.C. Lee, MD, Faculty of Medicine, University of Toronto; V.L. Fornasier, MD, Pathologist, Department of Pathology, St. Michael's Hospital; S.A. Berger, PhD, Arthritis and Immune Disorder Research Centre, University Health Network, Department of Immunology, University of Toronto. Address reprint requests to Dr. E.R. Bogoch, St. Michael's Hospital, 55 Queen Street East, Suite 800, Toronto, Ontario M5C 1R6. E-mail: bogoche@smh.toronto.on.ca Accepted for publication March 1, 2007. |
