Elevated serum kininogen in patients with Paget's disease of bone: a role in marrow stromal/preosteoblast cell proliferation.

Elevated serum kininogen in patients with Paget's disease of bone: a role in marrow stromal/preosteoblast cell proliferation. Research Abstract Details 

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Elevated serum kininogen in patients with Paget's disease of bone: a role in marrow stromal/preosteoblast cell proliferation. Abstract Text:

Eichi Tsuruga,D Sudhaker Rao,John E Baatz,Sakamuri V Reddy,

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.

Elevated serum kininogen in patients with Paget's disease of bone: a role in marrow stromal/preosteoblast cell proliferation. Publishing Authors By Initials

E Tsuruga,DS Rao,JE Baatz,SV Reddy,

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Elevated serum kininogen in patients with Paget's disease of bone: a role in marrow stromal/preosteoblast cell proliferation. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of cellular biochemistry

VOLUME: 98

Page Numbers: 1681-8

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ISSN: 0730-2312

DAY: 15

MONTH: Aug

YEAR: 2006

Elevated serum kininogen in patients with Paget's disease of bone: a role in marrow stromal/preosteoblast cell proliferation. Information

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LANGUAGE: eng

NlmUniqueID: 8205768

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AFFILIATION: Children's Research Institute, Medical University of South Carolina, Charleston, South Carolina, USA.

Country: United States

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MEDLINETA: J Cell Biochem

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