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Title: Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model

Abstract

This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a x 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsule with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.

Authors:
 [1];  [2];  [3];  [4];  [5]
  1. Department of Orthopaedic Surgery, School of Medicine, Catholic University of Deagu, 3056-6 Daemyung 4-Dong NamGu, Daegu, 705-718 (Korea, Republic of)
  2. Department of Anatomy, School of Medicine, Catholic University of Deagu, 3056-6 Daemyung 4-Dong NamGu, Daegu, 705-718 (Korea, Republic of)
  3. Internal Medicine, School of Medicine, Catholic University of Deagu, 3056-6 Daemyung 4-Dong NamGu, Daegu, 705-718 (Korea, Republic of)
  4. Radiology and Medical Engineering, School of Medicine, Catholic University of Deagu, 3056-6 Daemyung 4-Dong NamGu, Daegu, 705-718 (Korea, Republic of)
  5. Pohang Acceleratory Laboratory, Pohang University of Science and Technology, Pohang, 790-784 (Korea, Republic of)
Publication Date:
OSTI Identifier:
21043406
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 879; Journal Issue: 1; Conference: 9. international conference on synchrotron radiation instrumentation, Daegu (Korea, Republic of), 28 May - 2 Jun 2006; Other Information: DOI: 10.1063/1.2436456; (c) 2007 American Institute of Physics; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CAMERAS; CARTILAGE; CHARGE-COUPLED DEVICES; COMPARATIVE EVALUATIONS; CRYSTALS; IMAGES; MICE; MICROSCOPY; MICROSTRUCTURE; MONITORING; REFRACTION; REPUBLIC OF KOREA; RHEUMATIC DISEASES; SCINTILLATIONS; SPATIAL RESOLUTION; SYNCHROTRON RADIATION; X RADIATION; X-RAY DIFFRACTION

Citation Formats

Choi, Chang-Hyuk, Kim, Hong-Tae, Choe, Jung-Yoon, Kim, Jong Ki, and Youn, Hwa Shik. Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model. United States: N. p., 2007. Web. doi:10.1063/1.2436456.
Choi, Chang-Hyuk, Kim, Hong-Tae, Choe, Jung-Yoon, Kim, Jong Ki, & Youn, Hwa Shik. Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model. United States. doi:10.1063/1.2436456.
Choi, Chang-Hyuk, Kim, Hong-Tae, Choe, Jung-Yoon, Kim, Jong Ki, and Youn, Hwa Shik. Fri . "Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model". United States. doi:10.1063/1.2436456.
@article{osti_21043406,
title = {Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model},
author = {Choi, Chang-Hyuk and Kim, Hong-Tae and Choe, Jung-Yoon and Kim, Jong Ki and Youn, Hwa Shik},
abstractNote = {This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a x 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsule with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.},
doi = {10.1063/1.2436456},
journal = {AIP Conference Proceedings},
number = 1,
volume = 879,
place = {United States},
year = {Fri Jan 19 00:00:00 EST 2007},
month = {Fri Jan 19 00:00:00 EST 2007}
}
  • This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of (/sup 111/In)leukocytes. No accumulation of (/sup 111/In)leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by (/sup 111/In)leukocyte scintigraphy. There was little correlation between the stage of the disease, as determinedmore » by radiography, and (/sup 111/In)leukocyte accumulation. This study suggests that (/sup 111/In)leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response.« less
  • Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory and destructive joint disorder that affects tens of millions of people worldwide. Normal healthy joints maintain a balance between the synthesis of extracellular matrix (ECM) molecules and the proteolytic degradation of damaged ones. In the case of RA, this balance is shifted toward matrix destruction due to increased production of cleavage enzymes and the presence of (autoimmune) immunoglobulins resulting from an inflammation induced immune response. Herein we demonstrate that a polyclonal antibody against the proteoglycan biglycan (BG) causes tissue destruction that may be analogous to that of RA affected tissues. The effectmore » of the antibody is more potent than harsh chemical and/or enzymatic treatments designed to mimic arthritis-like fibril de-polymerization. In RA cases, the immune response to inflammation causes synovial fibroblasts, monocytes and macrophages to produce cytokines and secrete matrix remodeling enzymes, whereas B cells are stimulated to produce immunoglobulins. The specific antigen that causes the RA immune response has not yet been identified, although possible candidates have been proposed, including collagen types I and II, and proteoglycans (PG's) such as biglycan. We speculate that the initiation of RA associated tissue destruction in vivo may involve a similar non-enzymatic decomposition of collagen fibrils via the immunoglobulins themselves that we observe here ex vivo.« less
  • Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP andmore » wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G{sub 2}/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. - Highlights: • We studied how synovial fibroblasts accumulate in joints in a murine model of RA. • Bone marrow-derived cells did not accumulate in arthritic joints. • Synovial fibroblasts did not accumulate in arthritic joints via circulation. • Local proliferation was responsible for the synovial fibroblast accumulation.« less
  • The radiosensitivity of various components of serum rheumatoid factors was studied by exposing the factors in aqueous solutions to BETA radiation from added Na/sub 2/HP/sub 32/O/sub 4/ and to external gamma irradiation from a /sup 60/Co source. A new classification of rheumatoid factors is presented whereby they are considered in terms of four principal components; these are a hemagglutination factor which is responsible for the sensitized sheep cell reaction, a streptococcusagglutinating factor responsible for the L agglutination reaction, and two latex-agglutinating factors (1 and 2) which agglutinate latex particles sensitized with gamma globulin. Each of these four factors stimulated formationmore » of a specific antibody when they were injected in rabbits, and each factor could be further separated into agglutinating (a) and precipitating (p) fractions by ultrasonification. The a fractions of all four components were completely inactivated by exposure to 1 mC /sup 32/P for 3.25 to 3.75 hr, whereas the corresponding p fractions required only 1.5 to 84 min of exposure to the same amount of BETA radiation. Thus, the p fraction of latex factor 2 was 137 times more sensitive than the respective a fraction, and the p fraction of hemagglutination factor was 2.5 times more sensitive than the respective a fraction. When the factors were exposed to /sup 60/Co gamma radiation at a dose rate of 23 r/min, all four a fractions were completely inactivated in 4 to 5 hr, or after total doses of 5544 to 6237 r. In cortrast, the p fractions were inactivated after exposures of 11 to 44 sec, or 4.2 to 16.9 r. Thus, the gamma - ray sensitivity of p fractions was 369 to 1320 times greater than that of the corresponding a fractions. The heat sensitivities were also markedly greater for p than for a fractions of all four agglutination factors. (BBB)« less