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>Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet‐derived growth factor in osteoblast‐enriched cultures from fetal rat bone
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Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet‐derived growth factor in osteoblast‐enriched cultures from fetal rat bone
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机译：Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet‐derived growth factor in osteoblast‐enriched cultures from fetal rat bone
AbstractPlatelet‐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 systemically 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 with125I‐PDGF‐BB or125I‐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 ≈0.7 nM), less by PDGF‐AB (Ki ≈2.3 nM) and poorly by PDGF‐AA. In contrast,125I‐PDGF‐AA binding was measurably reduced by PDGF‐AA (Ki ≈4.0 nM), but was more effectively displaced by PDGF‐BB or PDGF‐AB (each with Ki ≈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
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