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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Endocrinology and Metabolism |
| Volume | 284 |
| Issue number | 5 47-5 |
| State | Published - May 1 2003 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - BMP-2 inhibits proliferation of human aortic smooth muscle cells via p21Cip1/Waf1
AU - Wong, Gail A.
AU - Tang, Vincent
AU - El-Sabeawy, Faten
AU - Weiss, Robert H
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
KW - Antisense
KW - Bone morphogenetic protein-2
KW - Vascular smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=0037403370&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037403370&partnerID=8YFLogxK
M3 - Article
C2 - 12527559
AN - SCOPUS:0037403370
VL - 284
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 5 47-5
ER -