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SOCS‐1/3 participation in FGF‐2 signaling to modulate RANK ligand expression in paget's disease of bone
Author(s) -
Sundaram Kumaran,
Senn Joseph,
Reddy Sakamuri V.
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24554
Subject(s) - stromal cell , rankl , osteoclast , bone resorption , fibroblast growth factor , bone marrow , cancer research , chemistry , biology , microbiology and biotechnology , endocrinology , medicine , immunology , activator (genetics) , receptor
ABSTRACT Paget's disease of bone (PDB) is a chronic focal skeletal disorder characterized by excessive bone resorption followed by disorganized new bone formation. Measles virus nucleocapsid (MVNP) is implicated in pathogenesis of PDB. RANK ligand (RANKL), a critical osteoclastogenic factor expressed on bone marrow stromal/preosteoblast cells is upregulated in PDB. We recently demonstrated that fibroblast growth factor‐2 (FGF‐2) which induces RANKL expression is elevated in PDB. In this study, we hypothesized that FGF‐2 modulates suppressors of cytokine signaling (SOCS) to induce RANKL expression in PDB. We identified increased levels of SOCS‐1/3 mRNA expression in bone marrow mononuclear cells derived from patients with PDB compared to normal subjects. Interestingly, conditioned media obtained from MVNP transduced osteoclast progenitor cells significantly increased SOCS‐1/3 mRNA expression in stromal/preosteoblast cells. We next examined if SOCS participates in FGF‐2 signaling to modulate RANKL gene expression. We showed that FGF‐2 stimulation significantly increased SOCS‐1/3 expression in human bone marrow stromal/preosteoblast cells. In addition, co‐expression of SOCS‐1/3 with hRANKL gene promoter‐luciferase reporter plasmid in marrow stromal cells demonstrated a significant increase in promoter activity without FGF‐2 stimulation. Furthermore, siRNA inhibition of STAT‐1 suppresses FGF‐2 increased SOCS‐1/3 expression in these cells. Thus, our results suggest that SOCS participates in FGF‐2 modulation of RANKL expression in PDB. J. Cell. Biochem. 114: 2032–2038, 2013. © 2013 Wiley Periodicals, Inc.