title: Osteocytes regulate primary lymphoid organs and fat metabolism.
abstract: Osteocytes act as mechanosensors to control local bone volume. However, their roles in the homeostasis of remote organs are largely unknown. We show that ablation of osteocytes in mice (osteocyte-less [OL] mice) leads to severe lymphopenia, due to lack of lymphoid-supporting stroma in both the bone marrow and thymus, and complete loss of white adipose tissues. These effects were reversed when osteocytes were replenished within the bone. In contrast, neither in vivo supply of T cell progenitors and humoral factors via shared circulation with a normal parabiotic partner nor ablation of specific hypothalamic nuclei rescued thymic atrophy and fat loss in OL mice. Furthermore, ablation of the hypothalamus in OL mice led to hepatic steatosis, which was rescued by parabiosis with normal mice. Our results define a role for osteocytes as critical regulators of lymphopoiesis and fat metabolism and suggest that bone acts as a central regulator of multiple organs.
authors.affiliation: Hematology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan; Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, North 13, West 7, Sapporo 060-8586, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Sato
authors.forename: Noboru
authors.initials: N
authors.lastname: Asada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawano
authors.forename: Kanako
authors.initials: K
authors.lastname: Wakahashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Minagawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawano
authors.forename: Akiko
authors.initials: A
authors.lastname: Sada
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D001284:Atrophy; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D060833:Cellular Microenvironment; D050356:Lipid Metabolism; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology*; D008231:Lymphopenia / Q000378:metabolism / Q000473:pathology; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D060168:Thymocytes / Q000378:metabolism / Q000473:pathology