Megakaryocyte-Bone Cell Interactions

  • Melissa A. KacenaEmail author
  • Wendy A. Ciovacco
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 658)


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.


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



bone marrow


bone marrow density


bone morphogenetic protein


bone marrow stromal cells


granulocyte/macrophage colony-stimulating factor


interferon gamma










osteoclast inhibitory lectin




platelet-derived growth factor


platelet-type von Willenbrand disease


receptor activator of nuclear factor kappa B ligand


transforming growth factor-β




tartrate resistant acid phosphatase


vascular endothelial growth factor



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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© 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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