Increase of Circulating CD11b+Gr1+ cells and
Recruitment into the Synovium in Osteoarthritic Mice with Hyperlipidemia |
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Authors: | Kentaro Uchida Kouji Naruse Masashi Satoh Kenji Onuma Masaki Ueno Shotaro Takano Ken Urabe Masashi Takaso |
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Institution: | 1)Department of Orthopedic Surgery, Kitasato University School of Medicine, 1–15–1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan;2)Department of Immunology, Kitasato University School of Medicine, 1–15–1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan |
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Abstract: | Although recent studies suggest that hyperlipidemia is a risk factor for osteoarthritis
(OA), the link between OA and hyperlipidemia is not fully understood. As the number of
activated, circulating myeloid cells is increased during hyperlipidemia, we speculate that
myeloid cells contribute to the pathology of OA. Here, we characterized myeloid cells in
STR/Ort mice, a murine osteoarthritis model, under hyperlipidemic conditions. Ratios of
myeloid cells in bone marrow, the spleen, and peripheral blood were determined by flow
cytometry. To examine the influence of the hematopoietic environment, including abnormal
stem cells, on the hematopoietic profile of STR/Ort mice, bone marrow transplantations
were performed. The relationship between hyperlipidemia and abnormal hematopoiesis was
examined by evaluating biochemical parameters and spleen weight of F2 animals
(STR/Ort x C57BL/6J). In STR/Ort mice, the ratio of CD11b+Gr1+ cells
in spleens and peripheral blood was increased, and CD11b+Gr1+ cells
were also present in synovial tissue. Splenomegaly was observed and correlated with the
ratio of CD11b+Gr1+ cells. When bone marrow from GFP-expressing mice
was transplanted into STR/Ort mice, no difference in the percentage of
CD11b+Gr1+ cells was observed between transplanted and age-matched
STR/Ort mice. Analysis of biochemical parameters in F2 mice showed that spleen
weight correlated with serum total cholesterol. These results suggest that the increase in
circulating and splenic CD11b+Gr1+ cells in STR/Ort mice originates
from hypercholesterolemia. Further investigation of the function of
CD11b+Gr1+ cells in synovial tissue may reveal the pathology of OA
in STR/Ort mice. |
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Keywords: | hyperlipidemia myelopoiesis osteoarthritis STR/Ort |
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