Megakaryocyte-Bone Cell Interactions

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 658)

Abstract

Emerging data show that megakaryocytes (MKs) play a role in the replication and development of bone cells. Both in vivo and in vitro evidence now show that MKs can have significant effects on cells of the osteoclast (OC) and osteoblast (OB) lineage, with obvious manifestations on bone phenotype, and probable significance for human pathology.

There are currently four mouse models in which increases in MK number lead to a specific bone pathology of markedly increased bone volume. While these models all achieve megakaryocytosis by different mechanisms, the resultant osteosclerotic phenotype observed is consistent across all models.

In vitro data suggest that MKs play a role in OC and OB proliferation and differentiation. While MKs express receptor activator of nuclear factor kappa B ligand (RANKL), a prerequisite for osteoclastogenesis, they also express many factors known to inhibit OC development, and co-cultures of MKs with OCs show a significant decrease in osteoclastogenesis. In contrast, MKs express several proteins with a known critical role in osteoblastogenesis and bone formation, and co-cultures of these two lineages result in up to a six-fold increase in OB proliferation and alterations in OB differentiation.

This research demonstrates the complex regulatory interactions at play between MKs and bone cells, and opens up potential targets for therapeutic intervention.

Keywords

Megakaryocyte Bone Osteoblast OsteoClast TPO NF-E2 GATA-1 Von Willenbrand 

Abbreviations

BM

bone marrow

BMD

bone marrow density

BMP

bone morphogenetic protein

BMSC

bone marrow stromal cells

GM-CSF

granulocyte/macrophage colony-stimulating factor

IFN-γ

interferon gamma

IL

interleukin

MK

megakaryocyte

OB

osteoblast

OC

osteoclast

OCIL

osteoclast inhibitory lectin

OPG

osteoprotegerin

PDGF

platelet-derived growth factor

Pt-vWD

platelet-type von Willenbrand disease

RANKL

receptor activator of nuclear factor kappa B ligand

TGF-β

transforming growth factor-β

TPO

thrombopoietin

TRAP

tartrate resistant acid phosphatase

VEGF

vascular endothelial growth factor

Notes

Acknowledgments

The authors wish to thank Dr. Amanda Taylor for her critical review of this study. This work was supported in part by NIH/NIAMS grant AR055269 (MAK).

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Orthopedics and RehabilitationYale University School of MedicineNew HavenUSA

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