Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor β1 mRNA expression

Noreen S. Cunningham, Vishwas Paralkar, A Hari Reddi

Research output: Contribution to journalArticle

228 Citations (Scopus)

Abstract

Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type β1 transforming growth factor (TGF-β1) in human monocytes. TGF-β1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-β are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-β1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.

Original languageEnglish (US)
Pages (from-to)11740-11744
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number24
StatePublished - 1992
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 3
Bone Morphogenetic Protein 4
Transforming Growth Factors
Recombinant Proteins
Monocytes
Messenger RNA
Bone Morphogenetic Proteins
Osteogenesis
Cytokines
Bone Matrix
Chemotactic Factors
Chemotaxis
Chemokines
Protein Binding
Extracellular Matrix
Collagen
Endothelial Cells
Macrophages
Binding Sites
Bone and Bones

Keywords

  • Bone induction
  • Bone repair
  • Cartilage
  • Developmental cascade

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{b38e4c95c8054862b9fcb9ca41f2d870,
title = "Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor β1 mRNA expression",
abstract = "Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type β1 transforming growth factor (TGF-β1) in human monocytes. TGF-β1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-β are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-β1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.",
keywords = "Bone induction, Bone repair, Cartilage, Developmental cascade",
author = "Cunningham, {Noreen S.} and Vishwas Paralkar and Reddi, {A Hari}",
year = "1992",
language = "English (US)",
volume = "89",
pages = "11740--11744",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "24",

}

TY - JOUR

T1 - Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor β1 mRNA expression

AU - Cunningham, Noreen S.

AU - Paralkar, Vishwas

AU - Reddi, A Hari

PY - 1992

Y1 - 1992

N2 - Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type β1 transforming growth factor (TGF-β1) in human monocytes. TGF-β1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-β are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-β1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.

AB - Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type β1 transforming growth factor (TGF-β1) in human monocytes. TGF-β1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-β are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-β1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade.

KW - Bone induction

KW - Bone repair

KW - Cartilage

KW - Developmental cascade

UR - http://www.scopus.com/inward/record.url?scp=0027074882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027074882&partnerID=8YFLogxK

M3 - Article

VL - 89

SP - 11740

EP - 11744

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 24

ER -