Involvement of integrins α3β1 and α5β1 and glycoprotein IIb in megakaryocyte-induced osteoblast proliferation

Justin M. Lemieux, Mark C. Horowitz, Melissa A. Kacena

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

As the prevalence of osteoporosis is expected to increase over the next few decades, the development of novel therapeutic strategies to combat this disorder becomes clinically imperative. These efforts draw extensively from an expanding body of knowledge pertaining to the physiologic mechanisms of skeletal homeostasis. To this body of knowledge, we contribute that cells of hematopoietic lineage may play a crucial role in balancing osteoblastic bone formation against osteoclastic resorption. Specifically, our laboratory has previously demonstrated that megakaryocytes (MKs) can induce osteoblast (OB) proliferation in vitro, but do so only when direct cell-to-cell contact is permitted. To further investigate the nature of this interaction, we have effectively neutralized several adhesion molecules known to function in the analogous interaction of MKs with another cell type of mesenchymal origin-the fibroblast (FB). Our findings implicate the involvement of fibronectin/RGD- binding integrins including α3β1 (VLA-3) and α5β1 (VLA-5) as well as glycoprotein (gp) IIb (CD41), all of which are known to be expressed on MK membranes. Furthermore, we demonstrate that interleukin (IL)-3 can enhance MK-induced OB activation in vitro, as demonstrated in the MK-FB model system. Taken together, these results suggest that although their physiologic and clinical implications are very different, these two models of hematopoietic-mesenchymal cell activation are mechanistically analogous in several ways.

Original languageEnglish (US)
Pages (from-to)927-932
Number of pages6
JournalJournal of Cellular Biochemistry
Volume109
Issue number5
DOIs
StatePublished - Apr 1 2010

Keywords

  • CD41
  • IL-3
  • Integrins
  • Megakaryocytes
  • Osteoblasts

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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