| First Author | Zhang Z | Year | 2005 |
| Journal | Biochem Biophys Res Commun | Volume | 328 |
| Issue | 3 | Pages | 800-7 |
| PubMed ID | 15694417 | Mgi Jnum | J:96168 |
| Mgi Id | MGI:3529634 | Doi | 10.1016/j.bbrc.2005.01.019 |
| Citation | Zhang Z, et al. (2005) Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient mice. Biochem Biophys Res Commun 328(3):800-7 |
| abstractText | Hematopoietic cell-specific disruption of the STAT3 gene induces hyperproliferation of cells of the myeloid lineage. Osteoclasts (OC), the bone-resorbing cells, are generated from the same precursors as monocyte/macrophages. STAT3 mutant mice exhibit decreased bone density, bone volume, and increased numbers of TRAP-positive OC. In vitro generation of OC showed significantly greater numbers of OC in mutant mice. The increased numbers of Mac1(+) cells and c-kit(+) cells were detected by FACS analysis, suggesting an increased number of OC precursors. Treatment of splenocytes with CSF-1 and RANKL significantly increased the Mac-1(+)RANK(+) cells, with much higher levels observed in cells from mutant mice compared with littermate controls. Besides enhanced number of Mac1(+) OC precursors, we also identified an OC-generating Mac1(-) c-kit(+) population in mutant mice which was absent in littermate controls. The Mac1(-) c-kit(-) cells did not generate OC. Finally, we determined that protein expression and mRNA level of c-fos, a transcription factor which is essential for OC differentiation, were enhanced in OC precursors of mutant mice, which may contribute to the osteopenic phenotype. |
