| First Author | Schulze-Späte U | Year | 2007 |
| Journal | J Cell Biochem | Volume | 102 |
| Issue | 1 | Pages | 1-12 |
| PubMed ID | 17668438 | Mgi Jnum | J:239205 |
| Mgi Id | MGI:5825429 | Doi | 10.1002/jcb.21257 |
| Citation | Schulze-Spate U, et al. (2007) Brn3 transcription factors control terminal osteoclastogenesis. J Cell Biochem 102(1):1-12 |
| abstractText | Osteoclastic bone resorption is a central mechanism in skeletal development, remodeling and pathology. RANKL is a mandatory factor controlling osteoclastogenesis; however, the underlying signaling pathways are only partially characterized. Using a screening array for the investigation of differential transcription factor activation, we identified activation of the Brn3 transcription factor family as a downstream event of RANKL signaling during terminal osteoclastogenesis. RANKL stimulation induces expression of Brn3a and b and maximal transcriptional activity of Brn3 family members concurrent with osteoclastic giant cell formation. Immunohistochemical analysis revealed both nuclear and cytoplasmic localization of Brn3a and b in mature osteoclasts. Functional inhibition of Brn3 transcription factors resulted in inhibition of pre-osteoclast fusion and reduction in bone resorbing activity of mature osteoclasts. Furthermore, we identified synaptotagmin-1, a regulator of membrane and vesicular fusion, as downstream target of Brn3 with a role in osteoclast function. We conclude that Brn-3 represents a novel molecular differentiation factor that controls osteoclast maturation and function, suggesting an important role in bone metabolism. |
