Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: similarity to estrogen deficiency.
Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated bone resorption by osteoclasts. During our investigations of the pathogenesis of bone loss in estrogen deficiency, we found that OVX selectively stimulates B-lymphopoiesis which results in marked accumulation of B220-positive pre-B cells in mouse bone marrow. To examine the possible correlation between stimulated B-lymphopoiesis and bone loss, 8-week-old female mice were treated with interleukin (IL) 7, which stimulates B-lymphopoiesis in bone marrow. We also examined bone mass in IL-7 receptor-knockout mice that exhibit marked suppression of B-lymphopoiesis in the bone marrow. The increased B-lymphopoiesis induced by IL-7 administration resulted in marked bone loss by stimulation of osteoclastic bone resorption in mice with intact ovarian function. The changes in both B-lymphopoiesis and bone mass in IL-7-treated female mice were similar to those in age-matched OVX mice. In contrast, the trabecular bone volume of the femur was greatly increased in both female and male IL-7 receptor-knockout mice when compared with the respective wild-type and heterozygous littermates. These results show that the perturbation of B-lymphopoiesis in the bone marrow is closely linked to the change in bone mass. We propose here that the increased B-lymphopoiesis due to estrogen deficiency is involved in the mechanism of stimulated bone resorption.
Miyaura
C
C
Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan.
Onoe
Y
Y
Inada
M
M
Maki
K
K
Ikuta
K
K
Ito
M
M
Suda
T
T
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology; D020395:Receptors, Interleukin-7
D015703:Antigens, CD; D004967:Estrogens; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7