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Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 (FGF23) by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-1α (HIF-1α) in other phosphate wasting disorders caused by elevated FGF23, including(More)
Insulin signaling in osteoblasts regulates global energy balance by stimulating the production of osteocalcin, a bone-derived protein that promotes insulin production and action. To identify the signaling pathways in osteoblasts that mediate insulin's effects on bone and energy metabolism, we examined the function of the tuberous sclerosis 2 (Tsc2) protein,(More)
Although angiogenesis and osteogenesis are critically linked, the importance of angiogenesis for stress fracture healing is unknown. In this study, mechanical loading was used to create a non-displaced stress fracture in the adult rat forelimb. Fumagillin, an anti-angiogenic agent, was used as the water soluble analogue TNP-470 (25mg/kg) as well as(More)
Alterations in resorption cavities and bone remodeling events during anti-resorptive treatment are believed to contribute to reductions in fracture risk. Here, we examine changes in the size of individual remodeling events associated with treatment with a selective estrogen receptor modulator (raloxifene) or a bisphosphonate (risedronate). Adult female rats(More)
Cavities formed by osteoclasts on the surface of cancellous bone during bone remodeling (resorption cavities) are believed to act as stress risers and impair cancellous bone strength and stiffness. Although resorption cavities are readily detected as eroded surfaces in histology sections, identification of resorption cavities in three-dimensional images of(More)
Serial block face imaging is a microscopy technique in which the top of a specimen is cut or ground away and a mosaic of images is collected of the newly revealed cross-section. Images collected from each slice are then digitally stacked to achieve 3D images. The development of fully automated image acquisition devices has made serial block face imaging(More)
Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anatomy, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature(More)
Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to(More)
Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb.(More)
HIF-1 is a transcription factor typically associated with angiogenic gene transcription under hypoxic conditions. In this study, mice with HIF-1α deleted in the osteoblast lineage (ΔHIF-1α) were subjected to damaging or non-damaging mechanical loading known to produce woven or lamellar bone, respectively, at the ulnar diaphysis. By microCT, ΔHIF-1α mice(More)