Osteoblastic Wnts differentially regulate bone remodeling and the maintenance of bone marrow mesenchymal stem cells.

Abstract

Wnt signaling has important roles in embryonic bone development and postnatal bone remodeling, but inconsistent impact on bone property is observed in different genetic alterations of Lrp5 and β-catenin. More importantly, it is still controversial whether Lrp5 regulate bone formation locally or globally through gut-derived serotonin. Here we explored the function of Wnt proteins in osteoblastic niche through inactivation of the Wntless (Wls) gene, which abrogates the secretion of Wnts. The depletion of Wls in osteoblast progenitor cells resulted in severe osteopenia with more profound defects in osteoblastogenesis, osteoclastogenesis and maintenance of bone marrow mesenchymal stem cells (BMSCs) compared to that observed in Lrp5 and β-catenin mutants. These findings support the point of view that Wnt/Lrp5 signaling locally regulates bone mass accrual through multiple effects of osteoblastic Wnts on osteoblastic bone formation and osteoclastic bone resorption. Moreover, osteoblastic Wnts confer a niche role for maintenance of BMSCs, providing novel cues for the definition of BMSCs niche in bone marrow.

• Authors: Yong Wan, Cheng Lu, Jingjing Cao, Rujiang Zhou, Yiyun Yao, Jian Yu, Lingling Zhang, Haixia Zhao, Hanjun Li, Jianzhi Zhao, Xuming Zhu, Lin He, Yongzhong Liu, Zhengju Yao, Xiao Yang, Xizhi Guo
• Journal: Bone (Bone) Vol. 55 Issue 1 Pg. 258-67 (Jul 2013) ISSN: 1873-2763 [Electronic] United States
• PMID: 23334081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Gpr177 protein, mouse
• Intracellular Signaling Peptides and Proteins
• RANK Ligand
• Receptors, G-Protein-Coupled
• Wnt Proteins
• Macrophage Colony-Stimulating Factor

Topics

• Animals
• Animals, Newborn
• Bone Diseases, Metabolic (diagnostic imaging, metabolism, pathology)
• Bone Marrow Cells (metabolism, pathology)
• Bone Remodeling
• Bone and Bones (diagnostic imaging, metabolism, pathology)
• Cell Differentiation
• Intracellular Signaling Peptides and Proteins (metabolism)
• Macrophage Colony-Stimulating Factor (metabolism)
• Mesenchymal Stem Cells (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Organ Size
• Osteoblasts (metabolism, pathology)
• Osteogenesis
• Paracrine Communication
• RANK Ligand (metabolism)
• Receptors, G-Protein-Coupled (metabolism)
• Wnt Proteins (metabolism)
• X-Ray Microtomography