Bone morphogenetic protein-7 (osteogenic protein-1) inhibits smooth muscle cell proliferation and stimulates the expression of markers that are characteristic of SMC phenotype in vitro

J Cell Physiol. 2000 Jul;184(1):37-45. doi: 10.1002/(SICI)1097-4652(200007)184:1<37::AID-JCP4>3.0.CO;2-M.


Vascular proliferative disorders are characterized by migration and proliferation of vascular smooth muscle cells (SMCs), loss of expression of SMC phenotype, and enhanced extracellular matrix synthesis (e.g., type I collagen). We report here that bone morphogenetic protein-7 (BMP-7), a member of the transforming growth factor-beta (TGF-beta) superfamily, is capable of inhibiting both serum-stimulated and growth factor-induced (platelet-derived growth factor [PDGF-BB] and TGF-beta1) cell growth as measured by (3)H-thymidine uptake into DNA synthesis and cell number in primary human aortic smooth muscle (HASM) cell cultures. Concomitantly, addition of BMP-7 stimulates the expression of SMC-specific markers, namely alpha-actin and heavy chain myosin as examined by RT-PCR and Northern blot analyses. The collagen type III/I ratio that becomes lower with the transdifferentiation of SMCs into myofibroblasts is also maintained in BMP-7-treated cultures as compared to untreated controls. Studies on the mechanism of action indicate that BMP-7 treatment inhibits cyclin-dependent kinase 2 (cdk-2) that was stimulated during PDGF-BB-induced proliferation of SMCs and upregulates the expression of the inhibitory Smad, Smad6, which was shown to inhibit TGF-beta superfamily signaling. These results collectively suggest that BMP-7 maintains the expression of vascular SMC phenotype and may prevent vascular proliferative disorders, thus potentially acting as a palliative after damage to the vascular integrity.

MeSH terms

  • Actins / genetics
  • Aorta
  • Apoptosis / drug effects
  • Becaplermin
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Protein Receptors, Type II
  • Bone Morphogenetic Proteins / pharmacology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Gene Expression Regulation / drug effects*
  • Humans
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Myosin Heavy Chains / genetics
  • Platelet-Derived Growth Factor / pharmacology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-sis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology


  • Actins
  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Transforming Growth Factor beta
  • Becaplermin
  • Protein Serine-Threonine Kinases
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II
  • Myosin Heavy Chains