biostudies-literatureMcGregor NEDepartment of Education and TrainingDepartment of Health | National Health and Medical Research Council7850-7863https://www.ebi.ac.uk/biostudies/studies/S-EPMC6514630biostudies-literatureUnknown294(19)Interleukin 6 (IL-6) supports development of bone-resorbing osteoclasts by acting early in the osteoblast lineage via membrane-bound (<i>cis</i>) or soluble (<i>trans</i>) receptors. Here, we investigated how IL-6 signals and modifies gene expression in differentiated osteoblasts and osteocytes and determined whether these activities can promote bone formation or support osteoclastogenesis. Moreover, we used a genetically altered mouse with circulating levels of the pharmacological IL-6 <i>trans</i>-signaling inhibitor sgp130-Fc to determine whether IL-6 <i>trans</i>-signaling is required for normal bone growth and remodeling. We found that IL-6 increases suppressor of cytokine signaling 3 (<i>Socs3</i>) and CCAAT enhancer-binding protein δ (<i>Cebpd</i>) mRNA levels and promotes signal trThe Journal of biological chemistryIL-6 exhibits both <i>cis</i>- and <i>trans</i>-signaling in osteocytes and osteoblasts, but only <i>trans</i>-signaling promotes bone formation and osteoclastogenesis.PMC6514630Project Grant 1081242Senior Research Fellowships 1019703 and 1154819Endeavour FellowshipElango JMurat MMartin TJSims NACrimeen-Irwin BHo PWMWalker ECMcGregor NEGooi JHPoulton IJfalseIL-6 exhibits both <i>cis</i>- and <i>trans</i>-signaling in osteocytes and osteoblasts, but only <i>trans</i>-signaling promotes bone formation and osteoclastogenesis.Interleukin 6 (IL-6) supports development of bone-resorbing osteoclasts by acting early in the osteoblast lineage via membrane-bound (<i>cis</i>) or soluble (<i>trans</i>) receptors. Here, we investigated how IL-6 signals and modifies gene expression in differentiated osteoblasts and osteocytes and determined whether these activities can promote bone formation or support osteoclastogenesis. Moreover, we used a genetically altered mouse with circulating levels of the pharmacological IL-6 <i>trans</i>-signaling inhibitor sgp130-Fc to determine whether IL-6 <i>trans</i>-signaling is required for normal bone growth and remodeling. We found that IL-6 increases suppressor of cytokine signaling 3 (<i>Socs3</i>) and CCAAT enhancer-binding protein δ (<i>Cebpd</i>) mRNA levels and promotes signal tr2019-01-01T00:00:00Z2019 May2025-04-04T07:57:48.113Z2025-04-04T07:57:48.113ZS-EPMC65146303092313010.1074/jbc.ra119.00807410.1074/jbc.RA119.008074