Osteogenic protein-1 downregulates endothelin A receptors in primary rat osteoblasts

Allison M. Kitten, Stephen A.K. Harvey, Nick Criscimagna, Megan Asher, John C. Lee, Merle S. Olson

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Osteogenesis is a complex process whereby growth factors and mediators from both local and systemic sources modulate the bone-forming activities of osteoblasts. In the present study we utilized primary cultures of fetal rat calvarial cells to characterize osteoblast responsiveness to the vascular mediator endothelin-1 (ET-1) and to investigate whether ET-1 responses are regulated by osteogenic protein-1 (OP-1). We found that a 1- to 2-day exposure to OP-1 diminished ET-1 receptor ligand binding and signal transduction by downregulating ET-1 receptor mRNA expression. ET-l-mediated calcium signaling and ligand binding were completely abolished by the ETA receptor antagonist BQ-123, suggesting that ET-1 effects are mediated by this receptor. Northern analysis of total RNA revealed that ETA mRNA expression was inhibited ~50% by OP-1 treatment, whereas ET(B) receptor mRNA was not detected by this method of analysis. In OP-l-treated cultures, the magnitude and duration of ET-1 calcium signals varied among individual cells. This finding may be related to a heterogeneous OP-1 response, indicated by alkaline phosphatase induction in only a subpopulation of cells. These results suggest that modulation of osteoblast function by ET-1 occurs during distinct periods of phenotypic development and imply that downregulation of ET-1 responsiveness may be necessary for optimal bone formation in vivo.

Original languageEnglish (US)
Pages (from-to)E967-E975
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6 35-6
StatePublished - Jun 1997


  • Bone
  • Bone morphogenetic proteins
  • Calcium signaling
  • Differentiation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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