title: Osteoprotegerin expression in bone marrow by treatment with tocilizumab in rheumatoid arthritis.
abstract: The aim of this study was to investigate histological changes of bone marrow in response to tocilizumab for rheumatoid arthritis (RA). After tocilizumab therapy, bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty (TKA). Control samples were obtained from ten RA patients who underwent MTX mono-therapy. Histological examination of structural differences between the tocilizumab and control groups in bone marrow was performed using hematoxylin and eosin (H&E) to evaluate differences. In immunohistochemical examination, the expression of seven molecules including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), CD68, osteoprotegerin (OPG), receptor activator of nuclear kappa B ligand (RANKL), CD4 and osteopontin (OPN) were compared between two groups. NTx was significantly low at 44.5 ± 2 nM BCE/mM Cr compared with control at 73.2 ± 8 nM BCE/mM Cr. Immunohistochemical examination revealed that the bone marrow tissues of the RA patients who underwent tocilizumab therapy demonstrated significant positive OPG as compared with the control. However, immunohistochemical examinations after tocilizumab revealed that TNF-α, IL-6, CD68, CD4, OPN and RANKL were not significantly different with control of MTX in bone marrow. Therefore, treatment with tocilizumab increased the expression of OPG as the histological changes with respect to inhibit RANKL-related bone resorption of bone marrow in RA.
authors.affiliation: Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo 116-8567, Japan. kanbeor@dnh.twmu.ac.jp
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Kanbe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Inoue
authors.forename: Kaori
authors.initials: K
authors.lastname: Hobo
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism*; D016022:Case-Control Studies; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018501:Antirheumatic Agents; D015415:Biomarkers; D015850:Interleukin-6; D008727:Methotrexate; D053495:Osteopontin; D053244:Osteoprotegerin; D053245:RANK Ligand; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C502936:tocilizumab