title: High-affinity binding of PDGF-AA and PDGF-BB to normal human osteoblastic cells and modulation by interleukin-1.
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.
authors.affiliation: Department of Oral Biology, Boston University Medical Center 02118.
authors.forename: R S
authors.initials: RS
authors.lastname: Gilardetti
authors.forename: M S
authors.initials: MS
authors.lastname: Chaibi
authors.forename: J
authors.initials: J
authors.lastname: Stroumza
authors.forename: S R
authors.initials: SR
authors.lastname: Williams
authors.forename: H N
authors.initials: HN
authors.lastname: Antoniades
authors.forename: D C
authors.initials: DC
authors.lastname: Carnes
authors.forename: D T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008024:Ligands; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D013936:Thymidine / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D013936:Thymidine