Megakaryocyte-Bone Cell Interactions
- Melissa A. KacenaAffiliated withDepartment of Orthopaedic Surgery, Indiana University School of Medicine Email author
- , Wendy A. CiovaccoAffiliated withDepartment of Orthopedics and Rehabilitation, Yale University School of Medicine
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.
KeywordsMegakaryocyte Bone Osteoblast OsteoClast TPO NF-E2 GATA-1 Von Willenbrand
- Megakaryocyte-Bone Cell Interactions
- Book Title
- Book Subtitle
- Interactions of the Immune and skeletal systems II
- pp 31-41
- Print ISBN
- Online ISBN
- Series Title
- Advances in Experimental Medicine and Biology
- Series Volume
- Series ISSN
- Springer US
- Copyright Holder
- Springer Science+Business Media, LLC
- Additional Links
- Von Willenbrand
- Industry Sectors
- eBook Packages
- Yongwon Choi (ID1)
- Editor Affiliations
- ID1. School of Medicine, University of Pennsylvania
- Author Affiliations
- 1. Department of Orthopaedic Surgery, Indiana University School of Medicine, 1120 South Drive, FH 115, 46202, Indianapolis, IN, USA
- 2. Department of Orthopedics and Rehabilitation, Yale University School of Medicine, 06520, New Haven, CT, USA
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