| First Author | Roberts JL | Year | 2020 |
| Journal | Ann N Y Acad Sci | Volume | 1463 |
| Issue | 1 | Pages | 45-59 |
| PubMed ID | 31919867 | Mgi Jnum | J:291961 |
| Mgi Id | MGI:6448591 | Doi | 10.1111/nyas.14293 |
| Citation | Roberts JL, et al. (2020) Deletion of Wnt5a in osteoclasts results in bone loss through decreased bone formation. Ann N Y Acad Sci 1463(1):45-59 |
| abstractText | Bone remodeling is achieved through the coupled activities of osteoclasts and osteoblasts that are controlled by many locally generated secreted factors, including WNT5A. While previous studies have demonstrated that osteoblast-derived WNT5A promotes osteoclastogenesis, the function of osteoclast-derived WNT5A on bone remodeling has remained unexplored. We examined the effects of osteoclast-derived WNT5A on bone homeostasis by utilizing the Cathepsin K-Cre (Ctsk-Cre) mouse to conditionally delete Wnt5a in mature osteoclasts. These mice exhibited reduced trabecular and cortical bone. The low bone-mass phenotype was driven by decreased bone formation, not osteoclast-mediated bone resorption, as osteoclast number and serum CTX marker were unchanged. Furthermore, molecular analysis of osteoclast- and osteoblast-derived WNT5A identified a serine-phosphorylated WNT5A that is unique to RANKL-treated macrophages mimicking osteoclasts. This study suggests a new paradigm in which WNT5A has opposing effects on bone remodeling that are dependent on the cell of origin, an effect that may result from cell type-specific differential posttranslational modifications of WNT5A. |
