High-affinity binding of PDGF-AA and PDGF-BB to normal human osteoblastic cells and modulation by interleukin-1

Am J Physiol. 1991 Dec;261(6 Pt 1):C980-5. doi: 10.1152/ajpcell.1991.261.6.C980.

Abstract

Bone has the capacity for repair and regeneration. The repair process is thought to be locally regulated by growth factors. One of the growth factors that potentially plays a significant role in these processes is platelet-derived growth factor (PDGF). Two different PDGF genes have been identified, PDGF-A and PDGF-B, whose gene products give rise to biologically active dimers. We now report that PDGF-AA and PDGF-BB exhibit saturable binding to normal human osteoblastic cells. By Scatchard analysis we estimate that there are approximately 43,000 PDGF-AA binding sites per cell, with a dissociation constant (Kd) of 2.2 x 10(-10)M, and 55,000 high-affinity PDGF-BB binding sites per cell, with a Kd of 1.2 x 10(-10)M. The functional consequence of PDGF binding was also assessed. PDGF-AA and PDGF-BB both stimulated migration of normal human osteoblastic cells and stimulated thymidine incorporation. To gain insight into potential transmodulation of the PDGF response, we investigated the capacity of interleukin-1 beta (IL-1 beta), a cytokine that induces bone resorption, to modulate PDGF binding and PDGF-induced biological activity. IL-1 beta significantly reduced PDGF-AA binding and significantly decreased both PDGF-AA-mediated cell migration and thymidine incorporation. In contrast, IL-1 beta had only a small effect of PDGF-BB binding and PDGF-BB-induced biological activity in normal human osteoblastic cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Movement
  • Cells, Cultured
  • Humans
  • Interleukin-1 / physiology*
  • Ligands
  • Middle Aged
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Platelet-Derived Growth Factor / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-sis
  • Thymidine / metabolism

Substances

  • Interleukin-1
  • Ligands
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • Thymidine