Murine Oncostatin M Acts via Leukemia Inhibitory Factor Receptor to Phosphorylate Signal Transducer and Activator of Transcription 3 (STAT3) but Not STAT1, an Effect That Protects Bone Mass
Emma C Walker, Rachelle W Johnson, Yifang Hu, Holly J Brennan, Ingrid J Poulton, Jian-Guo Zhang, Brendan J Jenkins, Gordon K Smyth, Nicos A Nicola, Natalie A Sims
JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2016
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are IL-6 family members with a wide range of biological functions. Human OSM (hOSM) and murine LIF (mLIF) act in mouse cells via a LIF receptor (LIFR)-glycoprotein 130 (gp130) heterodimer. In contrast, murine OSM (mOSM) signals mainly via an OSM receptor (OSMR)-gp130 heterodimer and binds with only very low affinity to mLIFR. hOSM and mLIF stimulate bone remodeling by both reducing osteocytic sclerostin and up-regulating the pro-osteoclastic factor receptor activator of NF-κB ligand (RANKL) in osteoblasts. In the absence of OSMR, mOSM still strongly suppressed sclerostin and stimulated bone formation but did not induce RANKL, suggesting..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) (Australia)
This work was supported in part by National Health and Medical Research Council (NHMRC) (Australia) Project Grants 1004945 (to N. A. S. and J.-G. Z.) and 1058625 (to N. A. S.) and Program Grant 1054618 (to G. K. S.). The authors declare that they have no conflicts of interest with the contents of this article.Supported by an NHMRC senior research fellowship.