Elevated serum kininogen in patients with paget's disease of bone: A role in marrow stromal/preosteoblast cell proliferation

✍ Scribed by Eichi Tsuruga; D. Sudhaker Rao; John E. Baatz; Sakamuri V. Reddy

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 192 KB
• Volume: 98
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20874

✦ Synopsis

Abstract

Paget's disease (PD) of bone is a chronic focal skeletal disorder characterized by excessive bone resorption followed by abundant new bone formation. Enhanced levels of IL‐6, RANKL, M‐CSF, and endothelin‐1 have been associated with PD. In the present study, we identified increased serum levels (2 to 5‐fold) of inflammatory cytokine, kininogen (KNG) in patients with PD compared to normal subjects. Treatment of pagetic bone marrow derived stromal/preosteoblast cells with recombinant KNG (25 ng/ml) for 24 h period resulted in a 5‐fold increase in the levels of phospho‐HSP27 and a 3‐fold increase in ERK1/2 phosphorylation in these cells. However, pagetic stromal cells stimulated with KNG in the presence of ERK activation inhibitor peptide did not significantly affect the levels of phospho‐HSP27. KNG increased normal and pagetic marrow stromal cell proliferation at 1.4‐fold and 2.5‐fold, respectively. KNG in the presence of an ERK inhibitor peptide did not stimulate pagetic marrow stromal cell proliferation. Furthermore, siRNA suppression of HSP27 expression significantly decreased KNG inhibition of etoposide‐induced caspase‐3 activation and apoptosis in these cells. In summary, KNG modulate bone marrow derived stromal/preosteoblast cell proliferation and suppress etoposide‐induced apoptosis through ERK and HSP27 activation, respectively. These results implicate a pathophysiologic role for KNG in patients with PD. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.