S24-3 Nuclear FGF2 Isoforms Inhibit Bone Marrow Stromal Cell Mineralization Through FGF23/FGFR/MAPK

Program: Symposia
Session: S24-FGF23: New Insight on Regulation in Humans and Murine Models
Basic
Sunday, June 16, 2013: 9:00 AM-10:30 AM
Presentation Start Time: 10:00 AM
Room 102 (Moscone Center)
Marja M Hurley*
Univ of Connecticut Health Ctr, Farmington, CT
Talk Description:

Fibroblast growth factor 23 (FGF23) is the phosphatonin responsible for phosphate wasting and the phenotypic changes observed in human disorders such as X-Linked Hypophosphatemia (XLH). Similar to FGF23, targeted over-expression of nuclear high molecular weight Fibroblast growth factor 2 isoforms (HMW) in osteoblasts resulted in a transgenic mouse with phenotypic changes similar to XLH including increased FGF23, hypophosphatemia and rickets/osteomalacia. We assessed whether HMW has phosphate independent effects to mediate reduced mineralized bone formation in vitro by modulating FGFR/FGF23/ERK signaling in bone marrow stromal cells (BMSCs). The decreased nodule formation in HMW cultures was partially rescued by FGF23 neutralizing antibody. Decreased nodule formation in HMW cultures was also partially rescued by FGF Receptor inhibitor SU5402 and MAP Kinase inhibitor PD98056. To determine the potential translational/clinical relevance we examined HMW expression in bones of Hyp mouse a murine homolog of XLH as well as HMW expression in lymphocytes from XLH patients.

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