Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone
- Department of Research, Saint Francis Hospital and Medical Center, Hartford, CT (USA)
Platelet-derived growth factor (PDGF) exists as a homodimer or a heterodimer comprising either PDGF-A or PDGF-B subunits, and each isoform occurs in various tissues, including bone. Although the stimulatory effects of PDGF-BB have been studied in cultures of bone cells and intact bone fragments, the influence of other isoforms that may arise locally or systematically in vivo, has not been reported. Therefore recombinant human PDGF-BB, PDGF-AB, and PDGF-AA were evaluated in osteoblast-enriched cultures from fetal rat bone. Within 24 hours these factors produced a graded response in bone cell DNA and protein synthesis, with half-maximal effects at approximately 0.6, 2.1, and 4.8 nM PDGF-BB, PDGF-AB, and PDGF-AA, respectively. Increases in collagen and noncollagen protein synthesis were abrogated when DNA synthesis was blocked with hydroxyurea. Furthermore, each factor reduced alkaline phosphatase activity, PDGF-BB being the most inhibitory. Binding studies with 125I-PDGF-BB or 125I-PDGF-AA and each unlabeled PDGF isoform produced discrete ligand binding and displacement patterns: 125I-PDGF-BB binding was preferentially displaced by PDGF-BB (Ki approximately 0.7 nM), less by PDGF-AB (Ki approximately 2.3 nM) and poorly by PDGF-AA. In contrast, 125I-PDGF-AA binding was measurably reduced by PDGF-AA (Ki approximately 4.0 nM), but was more effectively displaced by PDGF-BB or PDGF-AB (each with Ki approximately 0.7 nM). These studies indicate that each PDGF isoform produces biochemical effects proportional to binding site occupancy and suggest that receptors that favor PDGF-B subunit binding preferentially mediate these results in osteoblast-enriched bone cell cultures.
- OSTI ID:
- 5451865
- Journal Information:
- Journal of Cellular Physiology; (United States), Vol. 147:3; ISSN 0021-9541
- Country of Publication:
- United States
- Language:
- English
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GROWTH FACTORS
BIOCHEMICAL REACTION KINETICS
PROTEINS
BIOSYNTHESIS
ALKALINE PHOSPHATASE
BONE CELLS
CELL DIVISION
DNA
IODINE 125
MAN
PREGNANCY
PROLINE
RATS
TRACER TECHNIQUES
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
ESTERASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHATASES
PRIMATES
PYRROLES
PYRROLIDINES
RADIOISOTOPES
REACTION KINETICS
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques