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DOI: 10.1055/s-2006-924399
© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York
Serum Soluble Factors Induce the Proliferation, Alkaline Phosphatase Activity and Transforming Growth Factor-β Signal in Osteoblastic Cells in the Patient with Hepatitis C-associated Osteosclerosis
Publikationsverlauf
Received: January 4, 2006
First decision: April 3, 2006
Accepted: May 8, 2006
Publikationsdatum:
19. Dezember 2006 (online)
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Abstract
Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by severe, acquired, generalized osteosclerosis and hyperostosis in adults who are infected with the hepatitis C virus. However, the detail of the pathogenesis of HCAO is still unknown. We examined the effects of serum of the HCAO patient on the proliferation, alkaline phosphatase (ALP) activity and transforming growth factor (TGF)-β-Smad signaling in mouse osteoblastic cells. The patient was compatible with HCAO, characterized by high bone mass, bone thickening and bone pain with normal lamelar bone. The serum from the HCAO patient increased the levels of TGF-β and Smad3 expression in osteoblastic MC3T3-E1 cells, compared with the control subject. Moreover, the serum from the HCAO patient significantly augmented TGF-β-induced transcriptional activity with luciferase assay using 3TP-Lux with a Smad3-specific responsive element. In addition, the serum from the HCAO patient significantly stimulated the MTT intensity, the level of proliferating cell nuclear antigen expression, a proliferation marker, and ALP activity in MC3T3-E1 cells, compared with that from the control subject. In conclusion, the present study indicated that the serum from the HCAO patient stimulated TGF-β-Smad signaling, as well as the proliferation and ALP activity in osteoblastic cells. Some soluble factors other than parathyroid hormone might be related to the pathogenesis of HCAO.
Key words
Osteosclerosis TGF-β - osteoblast - smad3
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Correspondence
Dr. Hiroshi Kaji
Division of Endocrinology/Metabolism
Neurology and Hematology/Oncology
Department of Clinical Molecular Medicine
Kobe University Graduate School of Medicine
7-5-2 Kusunoki-cho
Chuo-ku
Kobe 650-0017
Japan
eMail: hiroshik@med.kobe-u.ac.jp