Ovariectomy fails to augment bone resorption and marrow B lymphopoiesis in granulocyte colony-stimulating factor transgenic mice.
The mechanism of pathological bone loss induced by estrogen deficiency has not been fully elucidated. It has been shown in recent animal studies that increased B lymphopoiesis induced by estrogen deficiency is involved in the mechanism of stimulated bone resorption. Mice transgenic for granulocyte colony-stimulating factor (G-CSF) (G-Tg) exhibit generalized osteopenia with an increase in osteoclast number and enhancement of bone resorption, which coexists with enhanced hematopoiesis. When ovariectomy was performed on G-Tg, it did not further reduce bone mass as revealed by radiography, dual-energy X-ray absorptiometry, and peripheral quantitative computed tomography. Ovariectomy increased the amount of colony-forming units of interleukin 7 (CFU-IL-7) by threefold in the marrow of normal mice in association with an increase in the number of B220-positive cells expressing the receptor activator of nuclear factor-kappaB ligand (RANKL). In contrast, the number of B220-positive cells expressing RANKL and CFU-IL-7 remarkably decreased in the marrow of G-Tg. Ovariectomy induced neither CFU-IL-7 nor B220-positive cells expressing RANKL in the marrow of G-Tg. Strong inhibition of B lymphopoiesis by G-CSF resulted in depletion of B cells expressing RANKL from the marrow, which may lead to resistance to bone loss due to ovariectomy. This observation suggests that B lymphopoiesis plays a possible role in bone loss in a condition of acute estrogen deficiency.
Oda
Takashi
T
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.
Wada
Takuro
T
Kuwabara
Hiroki
H
Sawada
Norimasa
N
Yamashita
Toshihiko
T
Kokai
Yasuo
Y
D000704:Analysis of Variance; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015519:Bone Density; D001854:Bone Marrow Cells / Q000502:physiology; D001862:Bone Resorption / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010052:Ovariectomy
D016179:Granulocyte Colony-Stimulating Factor