Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation
| Autor: | Jun Guo, Ernestina Schipani, Dehong Yang, Clare Thomas, F. Richard Bringhurst, Minlin Liu, Stuart Kuhstoss, Hiroaki Saito, R.J. Sells Galvin, Roland Baron, Henry M. Kronenberg, Mary L. Bouxsein |
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| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
Stromal cell Physiology HUMDISEASE Parathyroid hormone Osteoclasts Bone Marrow Cells Article Cell Line Mice Osteoclast Osteogenesis medicine Animals Humans RNA Messenger Molecular Biology Cells Cultured Cell Proliferation Hyperparathyroidism Osteoblasts Chemistry Wnt signaling pathway Osteoblast Cell Biology medicine.disease Mice Inbred C57BL Wnt Proteins medicine.anatomical_structure DKK1 Gene Expression Regulation Parathyroid Hormone Cancer research Intercellular Signaling Peptides and Proteins Signal transduction Stromal Cells hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Cell metabolism. 11(2) |
| ISSN: | 1932-7420 |
| Popis: | SummaryParathyroid hormone (PTH) suppresses Dickkopf 1 (Dkk1) expression in osteoblasts. To determine whether this suppression is essential for PTH-mediated Wnt signaling and bone formation, we examined mice that overexpress Dkk1 in osteoblasts (Dkk1 mice). Dkk1 mice were osteopenic due to abnormal osteoblast and osteoclast activity. When fed a low-calcium diet, and in two other models of hyperparathyroidism, these mice failed to develop the peritrabecular stromal cell response (“osteitis fibrosis”) and new bone formation seen in wild-type mice. Despite these effects of Dkk1 overexpression, PTH still activated Wnt signaling in Dkk1 mice and in osteoblastic cells cultured from these mice. In cultured MC3T3E1 preosteoblastic cells, PTH dramatically suppressed Dkk1 expression, induced PKA-mediated phosphorylation of β-catenin, and significantly enhanced Lef1 expression. Our findings indicate that the full actions of PTH require intact Wnt signaling but that PTH can activate the Wnt pathway despite overexpression of Dkk1. |
| Databáze: | OpenAIRE |
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