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Megakaryocyte-Bone Cell Interactions

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Osteoimmunology

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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

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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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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Indiana University School of Medicine, 1120 South Drive, FH 115, 46202, Indianapolis, IN, USA

    Melissa A. Kacena

  2. Department of Orthopedics and Rehabilitation, Yale University School of Medicine, 06520, New Haven, CT, USA

    Wendy A. Ciovacco

Authors
  1. Melissa A. Kacena
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  2. Wendy A. Ciovacco
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Correspondence to Melissa A. Kacena .

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Editors and Affiliations

  1. School of Medicine, University of Pennsylvania, Curie Blvd., Philadelphia, 19104, U.S.A.

    Yongwon Choi

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Kacena, M.A., Ciovacco, W.A. (2009). Megakaryocyte-Bone Cell Interactions. In: Choi, Y. (eds) Osteoimmunology. Advances in Experimental Medicine and Biology, vol 658. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1050-9_4

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