Scott A. Stewart

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Whether the negative impact of excess glucocorticoids on the skeleton is due to direct effects on bone cells, indirect effects on extraskeletal tissues, or both is unknown. To determine the contribution of direct effects of glucocorticoids on osteoblastic/osteocytic cells in vivo, we blocked glucocorticoid action on these cells via transgenic expression of(More)
Both aging and loss of sex steroids have adverse effects on skeletal homeostasis, but whether and how they may influence each others negative impact on bone remains unknown. We report herein that both female and male C57BL/6 mice progressively lost strength (as determined by load-to-failure measurements) and bone mineral density in the spine and femur(More)
UNLABELLED Mechanical stimulation of cultured osteocytic cells attenuates their apoptosis. We report here that, conversely, reduced mechanical forces in the murine model of unloading by tail suspension increases the prevalence of osteocyte apoptosis, followed by bone resorption and loss of mineral and strength. INTRODUCTION Mechanical loading is critical(More)
Because osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, increased adipogenesis may occur at the expense of osteoblasts, leading to bone loss. Our previous in vitro studies indicated that activation of the proadipogenic transcription factor peroxisome proliferator-activated receptor isoform gamma 2 with rosiglitazone(More)
We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand(More)
Glucocorticoids depress bone formation by inhibiting osteoblastogenesis and increasing osteoblast apoptosis. However, the role of bone resorption in the initial rapid phase of bone loss characteristic of glucocorticoid-induced osteoporosis is unexplained, and the reason for the efficacy of bisphosphonates in this condition remains unknown. We report that in(More)
Glucocorticoid administration to mice results in a rapid loss of bone mineral density due to an imbalance in osteoblast and osteoclast numbers. Whereas excess glucocorticoids reduce both osteoblast and osteoclast precursors, cancellous osteoclast number surprisingly does not decrease as does osteoblast number, presumably due to the ability of(More)
Hypogonadism has been implicated as a contributing factor in glucocorticoid-induced osteoporosis, but evidence for this is limited. Hypogonadism and glucocorticoid excess both cause bone loss, but the cellular mechanisms responsible are distinct. Loss of gonadal steroids causes an increase in bone remodeling by up-regulating osteoblastogenesis and(More)
Continuous elevation of parathyroid hormone (PTH) increases osteoclast precursors, the number of osteoclasts on cancellous bone, and bone turnover. The essential molecular mediators of these effects are controversial, however, and both increased receptor activator of NF-kappaB ligand (RANKL) and IL-6 have been implicated. The goal of these studies was to(More)
BACKGROUND Lymphatic function is critical for maintaining interstitial fluid balance and is linked to multiple pathological conditions. While smooth muscle contractile mechanisms responsible for fluid flow through collecting lymphatic vessels are well studied, how fluid flows into and through initial lymphatic networks remains poorly understood. The(More)