| First Author | Yang N | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 8 | Pages | e0181133 |
| PubMed ID | 28771604 | Mgi Jnum | J:247149 |
| Mgi Id | MGI:5915229 | Doi | 10.1371/journal.pone.0181133 |
| Citation | Yang N, et al. (2017) Role of glucocorticoid-induced leucine zipper (GILZ) in inflammatory bone loss. PLoS One 12(8):e0181133 |
| abstractText | TNF-alpha plays a key role in the development of rheumatoid arthritis (RA) and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs) also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ), a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-alpha-induced arthritic inflammation and protect bone in mice, we generated a TNF-alpha-GILZ double transgenic mouse line (TNF-GILZ Tg) by crossbreeding a TNF-alpha Tg mouse, which ubiquitously expresses human TNF-alpha, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3.6kb rat type I collagen promoter fragment. Results showed that overexpression of GILZ in bone marrow mesenchymal stem/progenitor cells protected mice from TNF-alpha-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-alphaTg, n = 12-15). However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-alpha-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines. |
