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Publication : Leukemia inhibitory factor treatment attenuates the detrimental effects of glucocorticoids on bone in mice.

First Author  Lee S Year  2021
Journal  Bone Volume  145
Pages  115843 PubMed ID  33429108
Mgi Jnum  J:305167 Mgi Id  MGI:6514936
Doi  10.1016/j.bone.2021.115843 Citation  Lee S, et al. (2021) Leukemia inhibitory factor treatment attenuates the detrimental effects of glucocorticoids on bone in mice. Bone 145:115843
abstractText  Glucocorticoids (GCs) are widely used drugs for the treatment of inflammatory and autoimmune diseases. However, a severe side effect induced by long-term GC therapy is osteoporosis. Leukemia inhibitory factor (LIF) - a glycoprotein 130 (gp130) dependent cytokine and member of the interleukin-6 cytokine family - is an activator protein 1 (AP-1) target gene that may be involved in one of the mechanisms underlying GC-induced bone loss. Indeed, we previously reported that the mRNA expression level of LIF was enhanced upon osteogenic differentiation, but was significantly decreased in GC-treated osteoblasts. In this study, we show that in vitro LIF treatment rescues the decreased early osteogenic differentiation and mineralization of GC-treated osteoblasts. Furthermore, we also demonstrate that in vivo LIF treatment protects against GC-mediated trabecular bone loss by decreasing the loss of both trabecular bone formation and osteoblast numbers. This protection appears to be conferred by LIF rescuing GC decreased activity of Stat3, MAPK, and Akt signaling pathways. Thus, the specific targeting of LIF signaling may represent a new therapeutic strategy to prevent GC-induced trabecular bone loss.
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