A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice

Monique Bethel, Calvin L T Barnes, Amanda F. Taylor, Ying Hua Cheng, Brahmananda R. Chitteti, Mark C. Horowitz, Angela Bruzzaniti, Edward Srour, Melissa Kacena

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Emerging data suggest that megakaryocytes (MKs) play a significant role in skeletal homeostasis. Indeed, osteosclerosis observed in several MK-related disorders may be a result of increased numbers of MKs. In support of this idea, we have previously demonstrated that MKs increase osteoblast (OB) proliferation by a direct cell-cell contact mechanism and that MKs also inhibit osteoclast (OC) formation. As MKs and OCs are derived from the same hematopoietic precursor, in these osteoclastogenesis studies we examined the role of the main MK growth factor, thrombopoietin (TPO) on OC formation and bone resorption. Here we show that TPO directly increases OC formation and differentiation in vitro. Specifically, we demonstrate the TPO receptor (c-mpl or CD110) is expressed on cells of the OC lineage, c-mpl is required for TPO to enhance OC formation in vitro, and TPO activates the mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and nuclear factor-kappaB signaling pathways, but does not activate the PI3K/AKT pathway. Further, we found TPO enhances OC resorption in CD14+CD110+ human OC progenitors derived from peripheral blood mononuclear cells, and further separating OC progenitors based on CD110 expression enriches for mature OC development. The regulation of OCs by TPO highlights a novel therapeutic target for bone loss diseases and may be important to consider in the numerous hematologic disorders associated with alterations in TPO/c-mpl signaling as well as in patients suffering from bone disorders.

Original languageEnglish
Pages (from-to)2142-2151
Number of pages10
JournalJournal of Cellular Physiology
Volume230
Issue number9
DOIs
StatePublished - Sep 1 2015

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Thrombopoietin
Human Development
Osteoclasts
Megakaryocytes
Bone
Thrombopoietin Receptors
Osteosclerosis
Janus Kinases
Bone Diseases
Osteoblasts
Mitogen-Activated Protein Kinase Kinases
Cell Lineage
Transcription
Bone Resorption
Mitogen-Activated Protein Kinases
Transducers
Phosphatidylinositol 3-Kinases
Osteogenesis
Blood Cells
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Bethel, M., Barnes, C. L. T., Taylor, A. F., Cheng, Y. H., Chitteti, B. R., Horowitz, M. C., ... Kacena, M. (2015). A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice. Journal of Cellular Physiology, 230(9), 2142-2151. https://doi.org/10.1002/jcp.24943

A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice. / Bethel, Monique; Barnes, Calvin L T; Taylor, Amanda F.; Cheng, Ying Hua; Chitteti, Brahmananda R.; Horowitz, Mark C.; Bruzzaniti, Angela; Srour, Edward; Kacena, Melissa.

In: Journal of Cellular Physiology, Vol. 230, No. 9, 01.09.2015, p. 2142-2151.

Research output: Contribution to journalArticle

Bethel M, Barnes CLT, Taylor AF, Cheng YH, Chitteti BR, Horowitz MC et al. A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice. Journal of Cellular Physiology. 2015 Sep 1;230(9):2142-2151. https://doi.org/10.1002/jcp.24943
Bethel, Monique ; Barnes, Calvin L T ; Taylor, Amanda F. ; Cheng, Ying Hua ; Chitteti, Brahmananda R. ; Horowitz, Mark C. ; Bruzzaniti, Angela ; Srour, Edward ; Kacena, Melissa. / A Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice. In: Journal of Cellular Physiology. 2015 ; Vol. 230, No. 9. pp. 2142-2151.
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