The Possible Role of TGF-β-Induced Suppressors of Cytokine Signaling Expression in Osteoclast/Macrophage Lineage Commitment In Vitro.
Date
2003-04-01Author
Subject
Metadata
Show full item recordAbstract
<jats:title>Abstract</jats:title> <jats:p>Osteoclast formation is dependent on the ability of TGF-β to enable receptor activator of NF-κB ligand (RANKL)-induced commitment of hemopoietic precursors to the osteoclastic lineage. The mechanism by which TGF-β enables formation is unknown. One possibility is that TGF-β opposes Janus kinase (JAK)/STAT signals generated by inhibitory cytokines such as IFN-β. The JAK/STAT pathway is activated by cytokines that induce resistance to osteoclast formation, such as IFN-γ and M-CSF, and the effect of these is opposed by TGF-β. Recently, a group of STAT-induced factors, termed suppressors of cytokine signaling (SOCS), has been identified that inhibit JAK/STAT signals. Therefore, we tested the ability of TGF-β to induce SOCS expression in osteoclast precursors and examined the effect of SOCS expression on osteoclast/macrophage lineage commitment. We found that while SOCS mRNA is undetectable in macrophages, osteoclasts express SOCS-3, and TGF-β up-regulates this expression. Furthermore, TGF-β rapidly induces sustained SOCS-3 expression in macrophage/osteoclast precursors. To determine whether SOCS-3 plays a role in osteoclast differentiation we expressed SOCS-3 in precursors using a retroviral system. We found that osteoclast differentiation was significantly enhanced in SOCS-3-infected precursors, and SOCS-3 expression enables formation in the presence of anti-TGF-β Ab. On the other hand, antisense knockdown of SOCS-3 strongly suppressed osteoclast formation and significantly blunted the response to TGF-β. Moreover, like TGF-β, SOCS-3 expression opposed the inhibitory effect of IFN-β. These data suggest that TGF-β-induced expression of SOCS-3 may represent a mechanism by which TGF-β suppresses inhibitory cytokine signaling, priming precursors for a role in bone resorption.</jats:p>
Collections
Publisher
Place of Publication
Journal
Volume
Issue
Pagination
Recommended, similar items
The following license files are associated with this item:
Related items
Showing items related by title, author, creator and subject.
-
Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells.
Harrington, LS; Sainson, RCA; Williams, CK; Taylor, JM; Shi, W; Li, J-L; Harris, AL (United States, 2008-03)The Notch ligand, Dll4, is essential for angiogenesis during embryonic vascular development and is involved in tumour angiogenesis. Several recent publications demonstrated that blockade of Dll4 signalling inhibits tumour ... -
Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response
Yang, Y; Willis, TL; Button, RW; Strang, CJ; Fu, Y; Wen, X; Grayson, PRC; Evans, T; Sipthorpe, RJ; Roberts, SL; Hu, Bing; Zhang, J; Lu, B; Luo, Shouqing (Springer Science and Business Media LLCEngland, 2019-08-21)<jats:title>Abstract</jats:title><jats:p>Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters intracellular aberrant proteins and mediates cargo delivery ... -
Molecular basis for Jagged-1/Serrate ligand recognition by the Notch receptor.
Whiteman, P; de Madrid, BH; Taylor, P; Li, D; Heslop, R; Viticheep, N; Tan, JZ; Shimizu, H; Callaghan, J; Masiero, M; Li, JL; Banham, AH; Harris, AL; Lea, SM; Redfield, C; Baron, M; Handford, PA (United States, 2013-03-08)We have mapped a Jagged/Serrate-binding site to specific residues within the 12th EGF domain of human and Drosophila Notch. Two critical residues, involved in a hydrophobic interaction, provide a ligand-binding platform ...