| First Author | Yu J | Year | 2016 |
| Journal | Bone | Volume | 84 |
| Pages | 38-46 | PubMed ID | 26688275 |
| Mgi Jnum | J:309576 | Mgi Id | MGI:6758325 |
| Doi | 10.1016/j.bone.2015.12.003 | Citation | Yu J, et al. (2016) Bone marrow fibrosis with fibrocytic and immunoregulatory responses induced by beta-catenin activation in osteoprogenitors. Bone 84:38-46 |
| abstractText | Wnt/beta-catenin signaling has been reported to contribute to the development of bone fibrous dysplasia. However, it remains unclear whether fibrocytes and immune cells are involved in this beta-catenin-mediated bone marrow fibrosis. In this study, we showed that constitutive activation of beta-catenin by Col1a1-Cre (3.6-kb) exhibited bone marrow fibrosis, featured with expanded populations of fibrocytes, myofibroblasts and osteoprogenitors. Lineage tracing and IHC examinations showed that Col3.6-Cre display Cre recombinase activity not only in osteoprogenitors, but also in monocyte-derived fibrocytes in the endosteal niches of bones. Additionally, beta-catenin stimulated the secretion of cytokines and pro-fibrotic signals in bone marrow, including GM-CSF, TGFbeta1 and VEGF. Consequently, the frequency of differentiated immature monocyte-derived dendritic cells and naive T cells was markedly increased in the mutant bone marrow. These phenotypes were quite different from those following beta-catenin activation in mature osteoblasts driven by Col1a1-Cre (2.3-kb). Our findings suggested that a conserved pro-fibrotic signal cascade might underlie beta-catenin-mediated bone marrow fibrosis, involving TGFbeta1-enhanced fibrocyte activation and immunoregulatory responses. This study might shed new light on the understanding and development of a therapeutic strategy for bone fibrous dysplasia. |
