R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression |
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Authors: | Lu Wenyan Kim Kyung-Ah Liu Jianzhong Abo Arie Feng Xu Cao Xu Li Yonghe |
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Affiliation: | Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255, USA. |
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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. |
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Keywords: | ALP, alkaline phosphatase CM, conditioned medium Dkk1, Dickkopf-1 LRP6, low density lipoprotein receptor-related protein 6 OCN, osteocalcin OPG, osteoprotegerin Rspo1, R-spondin 1 RANKL, receptor activator of NF-kappaB ligand |
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