FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2927572451> ?p ?o ?g. }

• W2927572451 endingPage "7863" @default.
• W2927572451 startingPage "7850" @default.
• W2927572451 abstract "Interleukin 6 (IL-6) supports development of bone-resorbing osteoclasts by acting early in the osteoblast lineage via membrane-bound (cis) or soluble (trans) 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 trans-signaling inhibitor sgp130-Fc to determine whether IL-6 trans-signaling is required for normal bone growth and remodeling. We found that IL-6 increases suppressor of cytokine signaling 3 (Socs3) and CCAAT enhancer-binding protein δ (Cebpd) mRNA levels and promotes signal transducer and activator of transcription 3 (STAT3) phosphorylation by both cis- and trans-signaling in cultured osteocytes. In contrast, RANKL (Tnfsf11) mRNA levels were elevated only by trans-signaling. Furthermore, we observed soluble IL-6 receptor release and ADAM metallopeptidase domain 17 (ADAM17) sheddase expression by osteocytes. Despite the observation that IL-6 cis-signaling occurs, IL-6 stimulated bone formation in vivo only via trans-signaling. Although IL-6 stimulated RANKL (Tnfsf11) mRNA in osteocytes, these cells did not support osteoclast formation in response to IL-6 alone; binucleated TRAP+ cells formed, and only in response to trans-signaling. Finally, pharmacological, sgp130-Fc–mediated inhibition of IL-6 trans-signaling did not impair bone growth or remodeling unless mice had circulating sgp130-Fc levels > 10 μg/ml. At those levels, osteopenia and impaired bone growth occurred, reducing bone strength. We conclude that high sgp130-Fc levels may have detrimental off-target effects on the skeleton. Interleukin 6 (IL-6) supports development of bone-resorbing osteoclasts by acting early in the osteoblast lineage via membrane-bound (cis) or soluble (trans) 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 trans-signaling inhibitor sgp130-Fc to determine whether IL-6 trans-signaling is required for normal bone growth and remodeling. We found that IL-6 increases suppressor of cytokine signaling 3 (Socs3) and CCAAT enhancer-binding protein δ (Cebpd) mRNA levels and promotes signal transducer and activator of transcription 3 (STAT3) phosphorylation by both cis- and trans-signaling in cultured osteocytes. In contrast, RANKL (Tnfsf11) mRNA levels were elevated only by trans-signaling. Furthermore, we observed soluble IL-6 receptor release and ADAM metallopeptidase domain 17 (ADAM17) sheddase expression by osteocytes. Despite the observation that IL-6 cis-signaling occurs, IL-6 stimulated bone formation in vivo only via trans-signaling. Although IL-6 stimulated RANKL (Tnfsf11) mRNA in osteocytes, these cells did not support osteoclast formation in response to IL-6 alone; binucleated TRAP+ cells formed, and only in response to trans-signaling. Finally, pharmacological, sgp130-Fc–mediated inhibition of IL-6 trans-signaling did not impair bone growth or remodeling unless mice had circulating sgp130-Fc levels > 10 μg/ml. At those levels, osteopenia and impaired bone growth occurred, reducing bone strength. We conclude that high sgp130-Fc levels may have detrimental off-target effects on the skeleton." @default.
• W2927572451 created "2019-04-11" @default.
• W2927572451 creator A5011945117 @default.
• W2927572451 creator A5019144368 @default.
• W2927572451 creator A5020882457 @default.
• W2927572451 creator A5035547433 @default.
• W2927572451 creator A5050766573 @default.
• W2927572451 creator A5051322126 @default.
• W2927572451 creator A5058592855 @default.
• W2927572451 creator A5060477938 @default.
• W2927572451 creator A5069853428 @default.
• W2927572451 creator A5082442667 @default.
• W2927572451 date "2019-05-01" @default.
• W2927572451 modified "2023-10-18" @default.
• W2927572451 title "IL-6 exhibits both cis- and trans-signaling in osteocytes and osteoblasts, but only trans-signaling promotes bone formation and osteoclastogenesis" @default.
• W2927572451 cites W1480870442 @default.
• W2927572451 cites W1508254430 @default.
• W2927572451 cites W1510936315 @default.
• W2927572451 cites W1537488315 @default.
• W2927572451 cites W1597588755 @default.
• W2927572451 cites W1968558772 @default.
• W2927572451 cites W1976402969 @default.
• W2927572451 cites W1982395713 @default.
• W2927572451 cites W1987996688 @default.
• W2927572451 cites W1989542542 @default.
• W2927572451 cites W1992814041 @default.
• W2927572451 cites W1996028579 @default.
• W2927572451 cites W1998111806 @default.
• W2927572451 cites W1999201913 @default.
• W2927572451 cites W2000659838 @default.
• W2927572451 cites W2003865675 @default.
• W2927572451 cites W2011683420 @default.
• W2927572451 cites W2015527055 @default.
• W2927572451 cites W2024171722 @default.
• W2927572451 cites W2036988498 @default.
• W2927572451 cites W2038036973 @default.
• W2927572451 cites W2038479043 @default.
• W2927572451 cites W2042623077 @default.
• W2927572451 cites W2044561904 @default.
• W2927572451 cites W2044726772 @default.
• W2927572451 cites W2046353810 @default.
• W2927572451 cites W2046396043 @default.
• W2927572451 cites W2051955486 @default.
• W2927572451 cites W2056995538 @default.
• W2927572451 cites W2057035809 @default.
• W2927572451 cites W2057436118 @default.
• W2927572451 cites W2060149005 @default.
• W2927572451 cites W2066385294 @default.
• W2927572451 cites W2069284462 @default.
• W2927572451 cites W2069284819 @default.
• W2927572451 cites W2071977541 @default.
• W2927572451 cites W2073788939 @default.
• W2927572451 cites W2073973087 @default.
• W2927572451 cites W2082236731 @default.
• W2927572451 cites W2082793765 @default.
• W2927572451 cites W2087665466 @default.
• W2927572451 cites W2093762042 @default.
• W2927572451 cites W2095546640 @default.
• W2927572451 cites W2105059159 @default.
• W2927572451 cites W2109608328 @default.
• W2927572451 cites W2117521006 @default.
• W2927572451 cites W2121265838 @default.
• W2927572451 cites W2121266814 @default.
• W2927572451 cites W2135575955 @default.
• W2927572451 cites W2145083090 @default.
• W2927572451 cites W2146200346 @default.
• W2927572451 cites W2152527598 @default.
• W2927572451 cites W2159555403 @default.
• W2927572451 cites W2170800098 @default.
• W2927572451 cites W2511863849 @default.
• W2927572451 cites W2583632111 @default.
• W2927572451 cites W2731047190 @default.
• W2927572451 cites W2762756467 @default.
• W2927572451 cites W2800189625 @default.
• W2927572451 cites W28773382 @default.
• W2927572451 cites W601907569 @default.
• W2927572451 doi "https://doi.org/10.1074/jbc.ra119.008074" @default.
• W2927572451 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6514630" @default.
• W2927572451 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30923130" @default.
• W2927572451 hasPublicationYear "2019" @default.
• W2927572451 type Work @default.
• W2927572451 sameAs 2927572451 @default.
• W2927572451 citedByCount "50" @default.
• W2927572451 countsByYear W29275724512019 @default.
• W2927572451 countsByYear W29275724512020 @default.
• W2927572451 countsByYear W29275724512021 @default.
• W2927572451 countsByYear W29275724512022 @default.
• W2927572451 countsByYear W29275724512023 @default.
• W2927572451 crossrefType "journal-article" @default.
• W2927572451 hasAuthorship W2927572451A5011945117 @default.
• W2927572451 hasAuthorship W2927572451A5019144368 @default.
• W2927572451 hasAuthorship W2927572451A5020882457 @default.
• W2927572451 hasAuthorship W2927572451A5035547433 @default.
• W2927572451 hasAuthorship W2927572451A5050766573 @default.
• W2927572451 hasAuthorship W2927572451A5051322126 @default.
• W2927572451 hasAuthorship W2927572451A5058592855 @default.
• W2927572451 hasAuthorship W2927572451A5060477938 @default.
• W2927572451 hasAuthorship W2927572451A5069853428 @default.

• next