TY - JOUR
T1 - Role of glucocorticoid-induced leucine zipper (GILZ) in inflammatory bone loss
AU - Yang, Nianlan
AU - Baban, Babak
AU - Isales, Carlos M.
AU - Shi, Xing Ming
N1 - Funding Information:
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health (https://www.nih.gov/ about-nih/what-we-do/nih-almanac/national-institute-aging-nia) under Award Numbers R01 AG046248 and P01 AG 036675. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01 AG046248 and P01 AG 036675.
PY - 2017/8
Y1 - 2017/8
N2 - TNF-α 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-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg) by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, 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-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12–15). However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.
AB - TNF-α 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-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg) by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, 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-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12–15). However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.
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U2 - 10.1371/journal.pone.0181133
DO - 10.1371/journal.pone.0181133
M3 - Article
C2 - 28771604
AN - SCOPUS:85026757796
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8
M1 - e0181133
ER -