Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.
Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 5-45 Yushima 1-Chome, Bunkyo-ku, Tokyo, 113-8510, Japan, ezura.mph@mri.tmd.ac.jp.
Yoichi
Y
Ezura
Junji
J
Nagata
Masashi
M
Nagao
Hiroaki
H
Hemmi
Tadayoshi
T
Hayata
Susan
S
Rittling
David T
DT
Denhardt
Masaki
M
Noda
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000166:cytology*; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D019070:Cell Lineage; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology; D019417:Hindlimb Suspension; D021621:Imaging, Three-Dimensional; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000378:metabolism; D053495:Osteopontin / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D055114:X-Ray Microtomography
D012333:RNA, Messenger; C506896:Spp1 protein, mouse; D053495:Osteopontin