Session: FP24-New Mechanisms in Bone Biology: From Cells to Genetics, & Mice to Men
Room 121 (Moscone Center)
Poster Board SUN-201
In the wild-type mice (WT, 12W), IGF-I treatment (50 mg/kg BW/day, 2 weeks) increased the number of vessels in the chondro-osseous junctions in the tibia. Immnohistochemical localization demonstrated that ephrin B2 was expressed in the endothelial cells and pericytes in the vessels in the long bones. In the global IGF-I KO mice, the expression of ephrin B2 was significantly decreased in the vessels of the tibia when compared to the WTs. To further investigate the role of IGF-I signaling in regulating vascularization, we generated mice with IGF-IR null mutation in the prehypertrophic chondrocytes (PHC), osteoprogentors and perichondium by crossing floxed IGF-IR mice with mice carrying the cre recombinase transgene under the control of osterix (OSX) promoter (osxIGF-IRKO). Histology showed that osxIGF-IRKO (3W) had fewer vessels in the secondary ossification center and chondro-osseous junctions in the tibia compared with controls. This was further confirmed by immunohistochemistry using an antibody against CD31. Immunohistochemical localization showed that ephrin B2 was expressed in chondrocytes, OBs, endothelial cells and pericytes in the tibia of the controls, but the expression was abolished in tibia of the osxIGF-IRKOs. Similarly, the expression of VEGF in the above cells was also reduced significantly in the osxIGF-IRKO. Quantitative real-time PCR analysis demonstrated that the mRNA (long bones, marrow flushed out) levels of ephrin B2 and EphB4 were significantly decreased in the osxIGF-IRKO (45% and 42% of the control, respectively). Our data indicate that IGF-I signaling in PHC, osteoprogenitors and perichondrium stimulates ephrin b2 production, which in turn to promotes vascularization in the primary and secondary ossification center during endochondral bone formation.
Nothing to Disclose: YW, AM, CF, DDB
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