Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) are major regulators of skeletal growth and development. Signal transduction via FGFRs is complex and mediates proliferation, differentiation, or migration depending upon the cellular context. Members of the Spry gene family antagonize the FGFR signal transduction pathway and inhibit lung morphogenesis, angiogenesis, and chondrogenesis. We examined the expression of Spry2 in the osteoblastic MC3T3-E1 cell line. MC3T3-E1 cells express Spry2 in response to FGF1 stimulation. Treatment of MC3T3-E1 cells with FGF1 results in the expression of Spry2 in a manner consistent with an early response gene. Pharmacological inhibitors of mitogen-activated protein kinase activation inhibit FGF1-induced expression of Spry2 mRNA. Transient overexpression of Spry2 in MC3T3-E1 resulted in decreased FGF1-mediated extracellular signal-regulated kinase phosphorylation and FGF1-stimulated osteopontin promoter activity. Furthermore, we show that Spry2 interacts with Raf-1 in a glutathione-S-transferase pulldown assay and that this interaction may involve multiple sites. Finally, Spry2 expression precedes the onset of the expression of osteoblast differentiation markers in an in vitro assay of primary osteoblast differentiation. Taken together, these results indicate that Spry2 expression is an early response to stimulation by FGF1 in MC3T3-E1 cells and acts as a feedback inhibitor of FGF1-induced osteoblast responses, possibly through interaction with Raf1.
Chimerism is defined as the presence of 2 or more than 1 genetically distinct cell populations in an organism. Dispermic chimeras are derived from the fertilization of 1 or 2 matured nuclei by 2 sperms. We here report detection of a healthy and phenotypically normal female with normal ABO red blood cell typing in whom dispermic chimerism was suspected after 3 alleles were identified at multiple human leukocyte antigen (HLA) loci using molecular HLA analysis. Molecular HLA typing showed the donor to have 3 HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles in blood, saliva and nail samples. In addition, 3 of her 9 short tandem repeat loci also showed to have 3 distinct alleles in blood, nail and saliva specimens. In all investigations, the third alleles were attributed to a dual paternal contribution. This case represents a dispermic chimerism, with 2 paternal and 1 maternal haplotypes variably distributed throughout body tissues in a healthy and phenotypically normal female without abnormalities in erythrocyte ABO blood group. The origin of this chimerism is probably due to the fertilization of a single egg and its polar body, or a parthenogenetic egg, by 2 sperms.
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