Abstract
R-spondins are a new group of Wnt/beta-catenin signaling agonists, however, the role of these proteins in bone remains unclear. We reported herein that R-sponin1 (Rspo1) acted synergistically with Wnt3A to activate Wnt/beta-catenin signaling in the uncommitted mesenchymal C2C12 cells. Furthermore, we found that Rspo1 at concentrations as low as 10 ng/ml synergized strongly with Wnt3A to induce C2C12 osteoblastic differentiation and osteoprotegerin expression. These events were blocked by Wnt/beta-catenin signaling antagonist Dickkopf-1. Finally, we demonstrated that Rspo1 synergized with Wnt3A to induce primary mouse osteoblast differentiation. Together, these findings suggest that Rpos1 may play an important role in bone remodeling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / metabolism
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Animals
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Animals, Newborn
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Cell Differentiation* / drug effects
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Cell Line
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Culture Media, Conditioned
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Gene Expression Regulation / drug effects
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Humans
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Intercellular Signaling Peptides and Proteins / metabolism
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LDL-Receptor Related Proteins / metabolism
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Low Density Lipoprotein Receptor-Related Protein-6
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Mice
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Osteoblasts / cytology*
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Osteoblasts / drug effects
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Osteoblasts / enzymology
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Osteoprotegerin / metabolism*
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Phosphorylation / drug effects
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Thermodynamics
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Thrombospondins / genetics
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Thrombospondins / metabolism*
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Thrombospondins / pharmacology
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Time Factors
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Wnt Proteins / metabolism*
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Wnt3 Protein
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Wnt3A Protein
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beta Catenin / metabolism
Substances
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Culture Media, Conditioned
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DKK1 protein, human
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Intercellular Signaling Peptides and Proteins
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LDL-Receptor Related Proteins
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LRP6 protein, human
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Low Density Lipoprotein Receptor-Related Protein-6
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Lrp6 protein, mouse
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Osteoprotegerin
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RSPO1 protein, human
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RSPO1 protein, mouse
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Thrombospondins
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WNT3A protein, human
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Wnt Proteins
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Wnt3 Protein
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Wnt3A Protein
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Wnt3a protein, mouse
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beta Catenin
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Alkaline Phosphatase