BMP-2 inhibits proliferation of human aortic smooth muscle cells via p21Cip1/Waf1

Gail A. Wong, Vincent Tang, Faten El-Sabeawy, Robert H Weiss

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Bone-morphogenetic proteins (BMP)-2 and -7, multifunctional members of the transforming growth factor (TGF)-β superfamily with powerful osteoinductive effects, cause cell cycle arrest in a variety of transformed cell lines by activating signaling cascades that involve several cyclin-dependent kinase inhibitors (CDKIs). CDKIs in the cip/kip family, p21Cip1/Waf1 and p27Kip1, have been shown to negatively regulate the G1 cyclins and their partner cyclin-dependent kinase proteins, resulting in BMP-mediated growth arrest. Bone morphogens have also been associated with antiproliferative effects in vascular tissue by unknown mechanisms. We now show that BMP-2-mediated inhibition of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cell (HASMC) proliferation is accompanied by increased levels of p21 protein. Antisense oligodeoxynucleotides specific for p21 attenuate BMP-2-induced inhibition of proliferation when transfected into HASMCs, demonstrating that BMP-2 inhibits PDGF-stimulated proliferation of HASMCs through induction of p21. Whether p21-mediated induction of cell cycle arrest by BMP-2 sets the stage for osteogenic differentiation of vascular smooth muscle cells, ultimately leading to vascular mineralization, remains to be investigated.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume284
Issue number5 47-5
StatePublished - May 1 2003

Fingerprint

Bone Morphogenetic Protein 2
Smooth Muscle Myocytes
Muscle
Cells
Cyclin-Dependent Kinases
Platelet-Derived Growth Factor
Cell Cycle Checkpoints
Blood Vessels
Cyclin G1
Bone Morphogenetic Protein 7
Transformed Cell Line
Bone Morphogenetic Proteins
Oligodeoxyribonucleotides
Cell proliferation
Transforming Growth Factors
Vascular Smooth Muscle
Bone
Cell Proliferation
Tissue
Bone and Bones

Keywords

  • Antisense
  • Bone morphogenetic protein-2
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

BMP-2 inhibits proliferation of human aortic smooth muscle cells via p21Cip1/Waf1 . / Wong, Gail A.; Tang, Vincent; El-Sabeawy, Faten; Weiss, Robert H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 284, No. 5 47-5, 01.05.2003.

Research output: Contribution to journalArticle

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