title: R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255, USA.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Lu
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Liu
authors.forename: Arie
authors.initials: A
authors.lastname: Abo
authors.forename: Xu
authors.initials: X
authors.lastname: Feng
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Li
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D053244:Osteoprotegerin / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013816:Thermodynamics; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000378:metabolism; D000098907:R-Spondins
chemical_list: D000469:Alkaline Phosphatase; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D053244:Osteoprotegerin; D019699:Thrombospondins; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; C501126:DKK1 protein, human; C555475:LRP6 protein, human; C555476:Lrp6 protein, mouse; C503243:RSPO1 protein, human; D000098907:R-Spondins; C518903:RSPO1 protein, mouse; C555510:WNT3A protein, human; C555511:Wnt3a protein, mouse