| First Author | Jie Z | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 3 | Pages | 4236-4247 |
| PubMed ID | 30526042 | Mgi Jnum | J:287877 |
| Mgi Id | MGI:6390303 | Doi | 10.1096/fj.201801977R |
| Citation | Jie Z, et al. (2019) Activating beta-catenin/Pax6 axis negatively regulates osteoclastogenesis by selectively inhibiting phosphorylation of p38/MAPK. FASEB J 33(3):4236-4247 |
| abstractText | Balance of osteoclast formation is regulated by the receptor activator of NF-kappaB ligand and extracellular negative regulators such as IFN-gamma and IFN-beta. However, very little is known about the intrinsic negative regulatory factors of osteoclast differentiation. Recently, the paired-box homeodomain transcription factor Pax6 was shown to negatively regulate receptor activator of NF-kappaB ligand-mediated osteoclast differentiation. However, the mechanism underlying this regulation is still unclear. In this study, we show that a p38 inhibitor (VX-745) up-regulates the expression of Pax6 during osteoclast differentiation. Subsequently, we found that beta-catenin could bind to the proximal region of Pax6 promoter to induce its expression, and this action could be impaired by p38-induced ubiquitin-mediated degradation of beta-catenin. Our results suggest that Pax6 is regulated by a novel p38/beta-catenin pathway. Pax6 can further regulate the nuclear translocation of NF of activated T cells, cytoplasmic 1. Our study indicates that this novel p38/beta-catenin/Pax6 axis contributes to negative regulation of osteoclastogenesis. In addition, our study proposes a novel approach to treat osteoclast-related diseases through the use of VX-745 complemented with the beta-catenin activator SKL2001.-Jie, Z., Shen, S., Zhao, X., Xu, W., Zhang, X., Huang, B., Tang, P., Qin, A., Fan, S., Xie, Z. Activating beta-catenin/Pax6 axis negatively regulates osteoclastogenesis by selectively inhibiting phosphorylation of p38/MAPK. |
