Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling.

Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)(+) mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans.

Simulated spaceflight produces a rapid and sustained loss of osteoprogenitors and an acute but transitory rise of osteoclast precursors in two genetic strains of mice.

Loss of skeletal weight bearing or skeletal unloading as occurs during spaceflight inhibits bone formation and stimulates bone resorption. These are associated with a decline in the osteoblast (Ob.S/BS) and an increase in the osteoclast (Oc.

Gs G protein-coupled receptor signaling in osteoblasts elicits age-dependent effects on bone formation.

Age-dependent changes in skeletal growth are important for regulating skeletal expansion and determining peak bone mass. However, how G protein-coupled receptors (GPCRs) regulate these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with high basal G(s) activity.

Osteoblast expression of an engineered Gs-coupled receptor dramatically increases bone mass.

Osteoblasts are essential for maintaining bone mass, avoiding osteoporosis, and repairing injured bone. Activation of osteoblast G protein-coupled receptors (GPCRs), such as the parathyroid hormone receptor, can increase bone mass; however, the anabolic mechanisms are poorly understood. Here we use "Rs1," an engineered GPCR with constitutive G(s) signaling, to evaluate the temporal and skeletal effects of G(s) signaling in murine osteoblasts.

IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone.

Unlabelled: We showed that the IGF-IR-null mutation in mature osteoblasts leads to less bone and decreased periosteal bone formation and impaired the stimulatory effects of PTH on osteoprogenitor cell proliferation and differentiation.

Introduction: This study was carried out to examine the role of IGF-I signaling in mediating the actions of PTH on bone.

Materials And Methods: Three-month-old mice with an osteoblast-specific IGF-I receptor null mutation (IGF-IR OBKO) and their normal littermates were treated with vehicle or PTH (80 microg/kg body weight/d for 2 wk).

Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading.

IGF-I stimulates osteoblast proliferation, bone formation, and increases bone volume in normal weight-bearing animals. During skeletal unloading or loss of weight bearing, bone becomes unresponsive to the anabolic effects of insulin-like growth factor I (IGF-I). To determine whether skeletal reloading after a period of unloading increases bone responsiveness to IGF-I, we examined bone structure and formation in response to IGF-I under different loading conditions.