A reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells

Melissa Kacena, Caren M. Gundberg, Mark C. Horowitz

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

A growing body of evidence suggests that megakaryocytes (MK) or their growth factors play a role in skeletal homeostasis. MK have been shown to express and/or secrete several bone-related proteins including osteocalcin, osteonectin, bone sialoprotein, osteopontin, bone morphogenetic proteins, and osteoprotegerin. In addition, at least 3 mouse models have been described in which MK number was significantly elevated with an accompanying marked increase in bone mineral density. Mice overexpressing thrombopoietin, the major MK growth factor, have an osteosclerotic bone phenotype. Mice deficient in transcription factors GATA-1 and NF-E2, which are required for the differentiation of MK, exhibited a strikingly increased bone mass. Importantly, recent studies have demonstrated that MK can stimulate osteoblast (OB) proliferation and differentiation in vitro and that they can also inhibit osteoclast (OC) formation in vitro. These findings suggest that MK play a dual role in skeletal homeostasis by stimulating formation while simultaneously inhibiting resorption. Conversely, cells of the osteoblast lineage support hematopoiesis, including megakaryopoiesis. Postnatal hematopoiesis occurs almost solely in the bone marrow (BM), close to or on endosteal surfaces. This finding, in conjunction with the observed contact of OB with hematopoietic cells, has lead investigators to explore the molecular and cellular interactions between hematopoietic cells and cells of the OB lineage. Importantly, it has been shown that many of the cytokines that are critical for normal hematopoiesis and megakaryopoiesis are produced by OB. Indeed, culturing osteoblasts with CD34+ BM cells significantly enhances hematopoietic cell number by both enhancing the proliferation of long-term culture initiating cells and the proliferation and differentiation of MK. These data are consistent with cells in the OB lineage playing a critical role in the hematopoietic niche. Overall, these observations demonstrate the importance of MK-bone cell interactions in both skeletal homeostasis and hematopoiesis.

Original languageEnglish (US)
Pages (from-to)978-984
Number of pages7
JournalBone
Volume39
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Megakaryocytes
Hematopoietic Stem Cells
Osteoblasts
Bone and Bones
Hematopoiesis
Homeostasis
Cell Lineage
Intercellular Signaling Peptides and Proteins
Osteonectin
GATA Transcription Factors
Integrin-Binding Sialoprotein
Thrombopoietin
Osteoprotegerin
Bone Morphogenetic Proteins
Osteopontin
Osteocalcin
Osteoclasts
Cell Communication
Bone Marrow Cells
Bone Density

Keywords

  • Bone formation
  • Hematopoiesis
  • Megakaryocytes
  • Megakaryopoiesis
  • Niche
  • Osteoblasts
  • Osteoclasts
  • Skeletal homeostasis

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

A reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells. / Kacena, Melissa; Gundberg, Caren M.; Horowitz, Mark C.

In: Bone, Vol. 39, No. 5, 11.2006, p. 978-984.

Research output: Contribution to journalArticle

Kacena, Melissa ; Gundberg, Caren M. ; Horowitz, Mark C. / A reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells. In: Bone. 2006 ; Vol. 39, No. 5. pp. 978-984.
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