Removal of the spleen in mice alters the cytokine expression profile of the marrow micro-environment and increases bone formation.
Splenectomized mice express progressively increased numbers of platelets in the blood and reduced numbers of megakaryocytes in the marrow with age. The megakaryocytes in the marrow of these animals express reduced levels of Gata1, a transcription factor necessary for their maturation. In addition, the marrow from these animals expresses greater levels of cytokines (TGF-beta, PDGF-alpha, and VEGF) known to be produced at high levels by megakaryocytes expressing reduced levels of Gata1. This high level of cytokine expression is in turn associated with active osteoblast proliferation localized to areas of the femur, where megakaryocytes expressing reduced Gata1 levels are also found. These results confirm the role of megakaryocytes as regulator of bone formation in mice and suggest that a cross-talk between the spleen and marrow may regulate the total numbers of hemopoietic niches present in an animal.
Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy.
Fabrizio
F
Martelli
Maria
M
Verrucci
Giovanni
G
Migliaccio
Maria
M
Zingariello
Rosa Alba
RA
Rana
Alessandro Maria
AM
Vannucchi
Anna Rita
AR
Migliaccio
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D001853:Bone Marrow / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D050982:GATA1 Transcription Factor / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000502:physiology*
D016207:Cytokines; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse