Anabolic and catabolic regimens of human parathyroid hormone 1-34 elicit bone- and envelope-specific attenuation of skeletal effects in Sost-deficient mice
| Autor: | Charles H. Turner, Alexander G. Robling, Teresita Bellido, Shana N. Ellis, Rajendra Kedlaya, Joseph P. Bidwell, Paul Childress |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Bone density Anabolism Bone and Bones Collagen Type I Mice Endocrinology Calcium-Regulating Hormones Bone Density Internal medicine Teriparatide Bone cell medicine Animals Humans Receptor Adaptor Proteins Signal Transducing Glycoproteins Catabolism Chemistry Peptide Fragments Resorption medicine.anatomical_structure Intercellular Signaling Peptides and Proteins Cortical bone Female Peptides hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Endocrinology. 152(8) |
| ISSN: | 1945-7170 |
| Popis: | PTH is a potent calcium-regulating factor that has skeletal anabolic effects when administered intermittently or catabolic effects when maintained at consistently high levels. Bone cells express PTH receptors, but the cellular responses to PTH in bone are incompletely understood. Wnt signaling has recently been implicated in the osteo-anabolic response to the hormone. Specifically, the Sost gene, a major antagonist of Wnt signaling, is down-regulated by PTH exposure. We investigated this mechanism by treating Sost-deficient mice and their wild-type littermates with anabolic and catabolic regimens of PTH and measuring the skeletal responses. Male Sost(+/+) and Sost(-/-) mice were injected daily with human PTH 1-34 (0, 30, or 90 μg/kg) for 6 wk. Female Sost(+/+) and Sost(-/-) mice were continuously infused with vehicle or high-dose PTH (40 μg/kg · d) for 3 wk. Dual energy x-ray absorptiometry-derived measures of intermittent PTH (iPTH)-induced bone gain were impaired in Sost(-/-) mice. Further probing revealed normal or enhanced iPTH-induced cortical bone formation rates but concomitant increases in cortical porosity among Sost(-/-) mice. Distal femur trabecular bone was highly responsive to iPTH in Sost(-/-) mice. Continuous PTH (cPTH) infusion resulted in equal bone loss in Sost(+/+) and Sost(-/-) mice as measured by dual energy x-ray absorptiometry. However, distal femur trabecular bone, but not lumbar spine trabecular bone, was spared the bone-wasting effects of cPTH in Sost(-/-) mice. These results suggest that changes in Sost expression are not required for iPTH-induced anabolism. iPTH-induced resorption of cortical bone might be overstimulated in Sost-deficient environments. Furthermore, Sost deletion protects some trabecular compartments, but not cortical compartments, from bone loss induced by high-dose PTH infusion. |
| Databáze: | OpenAIRE |
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